Search Antibody Database

Found 15 matching records:

Displaying record number 503

Download this epitope record as JSON.

MAb ID	50.1 (R/V3-50.1, Fab 50.1)
HXB2 Location	gp160(306-310) DNA(7140..7154)	gp160 Epitope Map
Author Location	gp120( MN)
Research Contact	Mary White-Scharf, Repligen Corporation, Cambridge, MA
Epitope	`RIHIG`	Epitope Alignment
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L
Species (Isotype)	mouse(IgG1κ)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, review, structure

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade MN
Vaccine component	Env V3

Notes

Showing 22 of 22 notes.

50.1: Data is summarized on the X-ray crystal structures resolution and NMR studies of 50.1. Sirois2007 (review, structure)
50.1: Angle of interaction between 50.1 and V3 was shown by superimposing the Fab fragment of the Ab with V3. Pantophlet2008 (antibody binding site, structure)
50.1: The crystal structure of V3-reactive antibody-peptide complexes were examined. 50.1 completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
50.1: This review summarizes data on crystallographic structures of 50.1 binding to its V3 peptide antigens. Conformation of the V3 peptide bound to 50.1 is very similar to its conformation when bound to 447-52D. Stanfield2005 (antibody binding site, review, structure)
50.1: NIH AIDS Research and Reference Reagent Program: 1289.
50.1: Called R/V3-50.1 -- A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain. Zhang2002
50.1: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding -- the dissociation constant, Kd of 50.1 for the cell associated primary and TCLA Envs was equal, 7nM. York2001
50.1: Called R/V3-50.1 -- six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes -- 50.1 could only neutralize the sensitive form. Park2000
50.1: The crystal structure of V3 loop peptides bound to Fabs was obtained -- conformational changes in the tip of the V3 loop (GPGR) were observed when different Fabs were bound. Stanfield1999
50.1: A T-cell line-adapted (TCLA) derivative of SI primary isolate 168P acquired the ability to be neutralized by anti-V3 MAbs -- the primary isolate could use either CCR5 or CXCR4, and was not neutralized when infection was directed via either pathway, however the TCLA derivative uses CXCR4 only and is neutralized. LaCasse1998
50.1: Binds to 6/7 isolates from breakthrough cases from a MN gp120 vaccine trial. Berman1997
50.1: Competition ELISAs with serial deletions produced comparable estimate of epitope length to crystal structure and alanine substitution -- KRIHIGP. Seligman1996
50.1: Used to monitor HIV-1 Env expression in infected H9 cells. VanCott1995
50.1: Shows modest cross-reactivity among B clade gp120s, little outside B clade. Moore1994b
50.1: Chimeric MN V3 loop in an HXB2 background allows increased FACS signal, Ab affinity, and viral neutralization. Database note: First author "Robert-Guroff" is also found as "RobertGuroff" on annotated papers in this database. Robert-Guroff1994
50.1: Potent MN neutralization, slow dissociation rate. VanCott1994
50.1: No neutralization of primary isolate JR-CSF -- greater affinity for and neutralization of T cell tropic strain T-CSF, derived from JR-CSF. Bou-Habib1994
50.1: Crystal structure of V3 loop bound to 50.1 -- light chain binds just to the left of GPG, heavy chain binds further to the left. Rini1993
50.1: Crystal structure of a 24 amino acid peptide from the V3 loop bound to 59.1 and 50.1 Fab fragments -- epitope KRIHIGP. Ghiara1993
50.1: No synergistic neutralization of MN when combined with CD4BS MAb F105 -- isotype stated to be IgG2a. Potts1993
50.1: Epitope defined by peptide reactivity and changes affinity with amino acid substitutions -- epitope RIHIGP. WhiteScharf1993 (antibody binding site, antibody generation)
50.1: Called R/V3-50.1 -- potent neutralizing of lab strains. DSouza1991

References

Showing 23 of 23 references.

Isolation Paper
WhiteScharf1993 M. E. White-Scharf, B. J. Potts, L. M. Smith, K. A. Sokolowski, J. R. Rusche, and S. Silver. Broadly Neutralizing Monoclonal Antibodies to the V3 Region of HIV-1 Can Be Elicited by Peptide Immunization. Virology, 192:197-206, 1993. Using a V3 loop peptide as immunogen, a panel of 50 anti-V3 neutralizing monoclonal antibodies were generated. Four of them were characterized in detail in this paper. PubMed ID: 7685962. Show all entries for this paper.

Berman1997 P. W. Berman, A. M. Gray, T. Wrin, J. C. Vennari, D. J. Eastman, G. R. Nakamura, D. P. Francis, G. Gorse, and D. H. Schwartz. Genetic and Immunologic Characterization of Viruses Infecting MN-rgp120-Vaccinated Volunteers. J. Infect. Dis., 176:384-397, 1997. PubMed ID: 9237703. Show all entries for this paper.

Bou-Habib1994 D. C. Bou-Habib, G. Roderiquez, T. Oravecz, P. W. Berman, P. Lusso, and M. A. Norcross. Cryptic Nature of Envelope V3 Region Epitopes Protects Primary Monocytotropic Human Immunodeficiency Virus Type 1 from Antibody Neutralization. J. Virol., 68:6006-6013, 1994. This paper shows that antibodies to the tip of the V3 loop fail to neutralize primary isolate JR-CSF, and that the V3 loop is far more accessible on the JR-CSF derived T-cell tropic strain T-CSF. Anti-V3 antibodies successfully neutralize T-CSF. Weak binding of anti-V3 antibodies to the primary isolate JR-CSF suggests the V3 loop is accessible only in a minor fraction of proteins. PubMed ID: 8057475. Show all entries for this paper.

DSouza1991 M. P. D'Souza, P. Durda, C. V. Hanson, G. Milman, and Collaborating Investigators. Evaluation of Monoclonal Antibodies to HIV-1 by Neutralization and Serological Assays: An International Collaboration. AIDS, 5:1061-1070, 1991. PubMed ID: 1718320. Show all entries for this paper.

Fontenot1995 J. D. Fontenot, T. C. VanCott, B. S. Parekh, C. P. Pau, J. R. George, D. L. Birx, S. Zolla-Pazner, M. K. Gorny, and J. M. Gatewood. Presentation of HIV V3 Loop Epitopes for Enhanced Antigenicity, Immunogenicity and Diagnostic Potential. AIDS, 9:1121-1129, 1995. PubMed ID: 8519447. Show all entries for this paper.

Ghiara1993 J. B. Ghiara, E. A. Stura, R. L. Stanfield, A. T. Profy, and I. A. Wilson. Crystal Structure of the Principal Neutralization Site of HIV-1. Science, 264:82-85, 1993. Crysal structure of V3 loop peptides bound to Fabs 59.1 and 50.1 was determined. The GPGRAF motif forms a double turn. PubMed ID: 7511253. Show all entries for this paper.

Hoffman1999 T. L. Hoffman, C. C. LaBranche, W. Zhang, G. Canziani, J. Robinson, I. Chaiken, J. A. Hoxie, and R. W. Doms. Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc. Natl. Acad. Sci. U.S.A., 96(11):6359--64, 25 May 1999. URL: http://www.pnas.org/cgi/content/full/96/11/6359. PubMed ID: 10339592. Show all entries for this paper.

Huang2005 Chih-chin Huang, Min Tang, Mei-Yun Zhang, Shahzad Majeed, Elizabeth Montabana, Robyn L. Stanfield, Dimiter S. Dimitrov, Bette Korber, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, and Peter D. Kwong. Structure of a V3-Containing HIV-1 gp120 Core. Science, 310(5750):1025-1028, 11 Nov 2005. PubMed ID: 16284180. Show all entries for this paper.

LaCasse1998 R. A. LaCasse, K. E. Follis, T. Moudgil, M. Trahey, J. M. Binley, V. Planelles, S. Zolla-Pazner, and J. H. Nunberg. Coreceptor utilization by human immunodeficiency virus type 1 is not a primary determinant of neutralization sensitivity. J. Virol., 72:2491-5, 1998. A T-cell line-adapted (TCLA) derivative of SI primary isolate 168P acquired the ability to to be neutralized by anti-V3 MAbs 257-D, 268-D and 50.1. The primary isolate could use either CCR5 or CXCR4, and was not neutralized when infection was directed via either pathway, but the TCLA derivative uses CXCR4 only and is neutralized. Thus coreceptor usage is not the primary determinant of differential neutralization sensitivity in primary versus TCLA strains. PubMed ID: 9499111. Show all entries for this paper.

Moore1994b J. P. Moore, F. E. McCutchan, S.-W. Poon, J. Mascola, J. Liu, Y. Cao, and D. D. Ho. Exploration of Antigenic Variation in gp120 from Clades A through F of Human Immunodeficiency Virus Type 1 by Using Monoclonal Antibodies. J. Virol., 68:8350-8364, 1994. Four of five anti-V3 MAbs were slightly cross-reactive within clade B, but not very reactive outside clade B. Two discontinuous CD4 binding site Mabs appear to be pan-reactive. Anti-V2 MAbs were only sporadically reactive inside and outside of clade B. PubMed ID: 7525988. Show all entries for this paper.

Pantophlet2008 Ralph Pantophlet, Terri Wrin, Lisa A. Cavacini, James E. Robinson, and Dennis R. Burton. Neutralizing Activity of Antibodies to the V3 Loop Region of HIV-1 gp120 Relative to Their Epitope Fine Specificity. Virology, 381(2):251-260, 25 Nov 2008. PubMed ID: 18822440. Show all entries for this paper.

Park2000 E. J. Park, M. K. Gorny, S. Zolla-Pazner, and G. V. Quinnan. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J. Virol., 74:4183-91, 2000. PubMed ID: 10756031. Show all entries for this paper.

Potts1993 B. J. Potts, K. G. Field, Y. Wu, M. Posner, L. Cavacini, and M. White-Scharf. Synergistic Inhibition of HIV-1 by CD4 Binding Domain Reagents and V3-Directed Monoclonal Antibodies. Virology, 197:415-419, 1993. Four anti-V3 loop MAbs, (59.1, 83.1, 50.1, and 58.2), were evaluated for their affinity, neutralization potencies, and their ability to synergize F105 or sCD4 neutralization. The most important parameter for synergy was the capacity to neutralize a given virus independently. PubMed ID: 8212576. Show all entries for this paper.

Rini1993 J. M. Rini, E. A. Stura, P. A. Salinas, A. T. Profy, and I. A. Wilson. Crystal Structure of a Human Immunodeficiency Virus Type 1 Neutralizing Antibody, 50.1, in Complex with its V3 Loop Peptide Antigen. Proc. Natl. Acad. Sci. U.S.A., 90:6325-6329, 1993. The V3 antigenic site is stretched out, not the $\beta$ turn seen as the primary determinant in other published anti-V3 peptide Fab structures. PubMed ID: 8327513. Show all entries for this paper.

Robert-Guroff1994 M. Robert-Guroff, A. Louie, M. Myagkikh, F. Michaels, M. P. Kieny, M. E. White-Scharf, B. Potts, D. Grogg, and M. S. Reitz, Jr. Alteration of V3 Loop Context within the Envelope of Human Immunodeficiency Virus Type 1 Enhances Neutralization. J. Virol., 68:3459-3466, 1994. MN-V3 loop inserted into a HBX2 background results in enhanced neutralization of anti-MN V3 MAb 50.1 and human HIV+ sera when the chimeric virus was compared to MN. Enhanced affinity, and greater proportions of labeled infected H9 cells by FACS analysis, were also observed using two anti-MN V3 MAbs, 50.1 and 83.1. PubMed ID: 7514675. Show all entries for this paper.

Seligman1996 S. J. Seligman, J. M. Binley, M. K. Gorny, D. R. Burton, S. Zolla-Pazner, and K. A. Sokolowski. Characterization by Serial Deletion Competition ELISAs of HIV-1 V3 Loop Epitopes Recognized by Monoclonal Antibodies. Mol. Immunol., 33:737-745, 1996. PubMed ID: 8811069. Show all entries for this paper.

Sirois2007 Suzanne Sirois, Mohamed Touaibia, Kuo-Chen Chou, and Rene Roy. Glycosylation of HIV-1 gp120 V3 Loop: Towards the Rational Design of a Synthetic Carbohydrate Vaccine. Curr. Med. Chem., 14(30):3232-3242, 2007. PubMed ID: 18220757. Show all entries for this paper.

Stanfield1999 R. Stanfield, E. Cabezas, A. Satterthwait, E. Stura, A. Profy, and I. Wilson. Dual Conformations for the HIV-1 gp120 V3 Loop in Complexes with Different Neutralizing Fabs. Structure, 7:131-142, 1999. PubMed ID: 10368281. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

VanCott1994 T. C. VanCott, F. R. Bethke, V. R. Polonis, M. K. Gorny, S. Zolla-Pazner, R. R. Redfield, and D. L. Birx. Dissociation Rate of Antibody-gp120 Binding Interactions Is Predictive of V3-Mediated Neutralization of HIV-1. J. Immunol., 153:449-459, 1994. Using surface plasmon resonance it was found that the rate of the dissociation of the MAb-gp120 complex, but not the association rate, correlated with MAbs ability to neutralize homologous virus (measured by 50\% inhibition of p24 production). Association constants were similar for all MAbs tested, varying less than 4-fold. Dissociation rate constants were quite variable, with 100-fold differences observed. PubMed ID: 7515931. Show all entries for this paper.

VanCott1995 T. C. VanCott, F. R. Bethke, D. S. Burke, R. R. Redfield, and D. L. Birx. Lack of Induction of Antibodies Specific for Conserved, Discontinuous Epitopes of HIV-1 Envelope Glycoprotein by Candidate AIDS Vaccines. J. Immunol., 155:4100-4110, 1995. The Ab response in both HIV-1 infected and uninfected volunteers immunized with HIV-1 rec envelope subunit vaccines (Genentech gp120IIIB, MicroGeneSys gp160IIIB, or ImmunoAG gp160IIIB) preferentially induced Abs reactive only to the denatured form of gp120. This may explain the inability of the vaccinee sera to neutralize primary HIV-1 isolates. PubMed ID: 7561123. Show all entries for this paper.

York2001 J. York, K. E. Follis, M. Trahey, P. N. Nyambi, S. Zolla-Pazner, and J. H. Nunberg. Antibody binding and neutralization of primary and T-cell line-adapted isolates of human immunodeficiency virus type 1. J. Virol., 75(6):2741--52, Mar 2001. URL: http://jvi.asm.org/cgi/content/full/75/6/2741. PubMed ID: 11222697. Show all entries for this paper.

Zhang2002 Peng Fei Zhang, Peter Bouma, Eun Ju Park, Joseph B. Margolick, James E. Robinson, Susan Zolla-Pazner, Michael N. Flora, and Gerald V. Quinnan, Jr. A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response. J. Virol., 76(2):644-655, Jan 2002. PubMed ID: 11752155. Show all entries for this paper.

Displaying record number 502

Download this epitope record as JSON.

MAb ID	83.1 (MAb 83.1)
HXB2 Location	gp160(309-315) DNA(7149..7169)	gp160 Epitope Map
Author Location	gp120( SF2)
Research Contact	Mary White-Scharf, Repligen Corporation, Cambridge, MA
Epitope	`IYIGPGR`	Epitope Alignment
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L
Species (Isotype)	mouse(IgG1)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, review, structure

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade MN
Vaccine component	Env V3

Notes

Showing 9 of 9 notes.

83.1: Data is summarized on the X-ray crystal structures resolution and NMR studies of 83.1. Sirois2007 (review, structure)
83.1: Angle of interaction between 83.1 and V3 was shown by superimposing the Fab fragment of the Ab with V3. Pantophlet2008 (antibody binding site, structure)
83.1: The crystal structure of V3-reactive antibody-peptide complexes were examined. 83.1 completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
83.1: This review summarizes data on crystallographic structures of 83.1 binding to its V3 peptide antigens. Conformation of the V3 peptide bound to 83.1 is very similar to its conformation when bound to 447-52D. Stanfield2005 (antibody binding site, review, structure)
83.1: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes. Binley2000
83.1: 19 day old mice injected with 83.1 have a shift in IgG1 response away from the V3 loop upon vaccination, without decreasing the total IgG anti-gp120 response, suggesting that prior treatment with a MAb can mask immunogenic sites and shift the immune response to vaccination. Keller1999
83.1: Maternally transferred anti-V3 loop MAb selectively inhibits the anti-V3 loop Ab component of the IgG response to rgp120 SF2 in 21 day old BALBc mice. Jelonek1996
83.1: Study of synergism of neutralization and binding comparing F105 and sCD4 with the V3 MAbs: 50.1, 59.1, 83.1, and 58.2 -- synergy was observed, and the data suggest that binding of one ligand (F105) can increase the binding of the second (e. g. V3 loop MAbs) due to conformational changes. Potts1993
83.1: Neutralizes SF2. WhiteScharf1993 (antibody generation)

References

Showing 9 of 9 references.

Binley2000 J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724. Show all entries for this paper.

Jelonek1996 M. Jelonek, J. Maskrey, K. Steimer, B. Potts, K. Higgins, and M. Kellor. Maternal Monoclonal Antibody to the V3 Loop Alters Specificity of the Response to a Human Immunodeficiency Virus Vaccine. J. Infect. Dis., 174:866-869, 1999. PubMed ID: 8843232. Show all entries for this paper.

Keller1999 M. Keller and Y. Arora. Inhibition of Anti-V3 Loop Response to a Recombinant gp120 SF2 Vaccine Be Preexisting Monoclonal Ab. AIDS Res. Hum. Retroviruses, 15:855-860, 1999. PubMed ID: 10381174. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

Displaying record number 457

Download this epitope record as JSON.

MAb ID	19b (N70-1.9b, N701.9b, 1.9B)
HXB2 Location	gp160(309-320) DNA(7149..7184)	gp160 Epitope Map
Author Location	gp120
Research Contact	James Robinson, University of Connecticut, Storrs
Epitope	`SVHIGPGQAFYAT, SIHIGPGRAFYTT, SIRIGPGQTFYAT, RTHIGPQALYT T, SITIGPGQVFYRT, SIHLGPGQAFYAT`	Epitope Alignment
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L
Species (Isotype)	human(IgG1κ)
Patient	N70
Immunogen	HIV-1 infection
Keywords	ADCC, antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, assay or method development, autoantibody or autoimmunity, binding affinity, broad neutralizer, glycosylation, neutralization, novel epitope, optimal epitope, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 65 of 65 notes.

19b: Soluble versions of HIV-1 Env trimers (sgp140 SOSIP.664) stabilized by a gp120-gp41 disulfide bond and a change (I559P) in gp41 have been structurally characterized. Cross-linking/mass spectrometry to evaluate the conformations of functional membrane Env and sgp140 SOSIP.664 has been reported. Differences were detected in the gp120 trimer association domain and C terminus and in the gp41 HR1 region which can guide the improvement of Env glycoprotein preparations and potentially increasing their effectiveness as a vaccine. 19b targeted gp120 V3 loop and exhibited poor neutralization against HIV-1AD8 full-length and cytoplasmic tail-deleted Envs. Castillo-Menendez2019 (vaccine antigen design, structure)
19b: The influence of a V2 State 2/3-stabilizing Env mutation, L193A, on ADCC responses mediated by sera from HIV-1-infected individuals was evaluated. Conformations spontaneously sampled by the Env trimer at the surface of infected cells had a significant impact on ADCC. State 2/3 preferring ligand 19b recognized L193A variants of CH58 and CH77 IMCs with a significant increase compared to the WT. Prevost2018 (ADCC)
19b: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 19b globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with the exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
19b: Assays of poly- and autoreactivity demonstrated that broadly neutralizing NAbs are significantly more poly- and autoreactive than non-neutralizing NAbs. 19b is neither autoreactive nor polyreactive. Liu2015a (autoantibody or autoimmunity, antibody polyreactivity)
19B: The study identified a HIV-1–neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by monoclonal antibodies that bind to the V3 loop (19B and F39F) and chemokine coreceptor binding site (17B). Fouda2013 (antibody binding site)
19b: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. For 19b the non-NAb epitope did not depend on residues 306 and 308. deTaeye2018 (broad neutralizer)
19b: Nanodiscs (discoidal lipid bilayer particles of 10-17 nm surrounded by membrane scaffold protein) were used to incorporate Env complexes for the purpose of vaccine platform generation. The Env-NDs (Env-NDs) were characterized for antigenicity and stability by non-NAbs and NAbs. Most NAb epitopes in gp41 MPER and in the gp120:gp41 interface were well exposed while non-NAb cell surface epitopes were generally masked. Anti-V3 variable non-NAb 19b, binds at a fraction of the binding of 2G12 to Env-ND, and this binding is sensitive to glutaraldehyde treatment . Witt2017 (vaccine antigen design, binding affinity)
19b: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens. Johnson2017 (vaccine antigen design)
19b: The results confirm that Nef and Vpu protect HIV-1-infected cells from ADCC, but also show that not all classes of antibody can mediate ADCC. Anti-cluster-A antibodies are able to mediate potent ADCC responses, whereas anti-coreceptor binding site antibodies are not. Position 69 in gp120 is important for antibody-mediated cellular toxicity by anti-cluster-A antibodies. The angle of approach of a given class of antibodies could impact its capacity to mediate ADCC. Mabs 19b and GE2-JG8 were used as anti-V3 Abs; they did not mediate strong ADCC activity. Ding2015 (ADCC)
19b: To understand HIV neutralization mediated by the MPER, antibodies and viruses were studied from CAP206, a patient known to produce MPER-targeted neutralizing mAbs. 41 human mAbs were isolated from CAP206 at various timepoints after infection, and 4 macaque mAbs were isolated from animals immunized with CAP206 Env proteins. Two rare, naturally-occuring single-residue changes in Env were identified in transmitted/founder viruses (W680G in CAP206 T/F and Y681D in CH505 T/F) that made the viruses less resistant to neutralization. The results point to the role of the MPER in mediating the closed trimer state, and hence the neutralization resistance of HIV. 19b was one of several mAbs tested for neutralization of transmitted founder viruses isolated from clade C infected individuals CAP206 and CH505, compared to T/F viruses containing MPER mutations that confer enhanced neutralization sensitivity. Bradley2016a (neutralization)
19B: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson
19b: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing V3 Ab, 19b did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate though it did bind gp160 minus its C-terminus (gp160ΔCT) moderately, and was able to bind in the presence of sCD4. Chen2015 (neutralization, binding affinity)
19b: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41_ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC₅₀ >50µg/ml). Pugach2015
19b: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes against all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. The Clade C trimers are weakly reactive with the non-NAb, 19b. Julien2015 (assay or method development, structure)
19b: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of anti-V3 non-NAb 19b to trimers was reduced by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
19b: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 19b did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself. Sanders2013 (assay or method development, neutralization, binding affinity)
19b: A panel of Env-specific mAbs was isolated from 6 HIV1-infected lactating women. Antibodies in colostrum may help prevent mucosal infection of the infant, so this study aimed to define milk IgGs for future vaccination strategies to reduce HIV transmission during lactation. Despite the high rate of VH 1-69 usage among colostrum Env specific B cells, it did not correlate with distinct gp120 epitope specificity or function. 19b was compared to the newly-derived mAbs; it tested positive in one assay of cross-reactivity with gut bacteria, and positive in one test of autoreactivity. Jeffries2016 (antibody polyreactivity)
19b: The study detailed binding kinetics of the interaction between BG505 SOSIP.664 trimer or its variants (gp120 monomer; first study of disulfide-stabilized variant gp120-gp41_ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). V3-specific 19b does not neutralize BG505.T332N pseudovirus, but binds strongly to monomer, substantially less to protomer, and negligibly to trimer. Yasmeen2014 (antibody binding site, assay or method development)
19b: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
N70-1.9b: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates. Gorny2003 (review)
N70-1.9b: Type specificity. Antibody generation. Robinson1990c (antibody generation, variant cross-reactivity)
Lists 7 mAbs derived from patient N70: 15E, 1.9B, 2.3A, 2.3B, 2.1H, F91, 1.7B. Robinson1992
N70-1.9b: Type specific neutralization, ADCC directed against MN infected cells. Scott1990 (ADCC, variant cross-reactivity)
19b: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. MAb 19b bound more strongly to deglycosylated trimers than untreated ones. Depetris2012 (glycosylation, binding affinity)
19b: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. Externally exposed residues of gp120 that participated in stabilizing interaction with the aptamer were mutated. Binding of 19b to gp120 was enhanced by B40t77, which is suggested to be due to distant conformational changes of gp120 induced by the aptamer. Joubert2010 (binding affinity, structure)
19b: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 19b bound better to all uncleaved ΔV1V2 variants than to the full-length trimer, and bound similarly to the cleaved ΔV1V2 and full-length variants. Bontjer2010 (binding affinity)
19b: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. Binding of 19b to gp120 or to the V3 peptide alone of CC101.19 was greater than to gp120 or the V3 peptide of the three other viruses. 19b neutralized CC101.19 but did not neutralize the other three viruses. This indicates that the V3 region of CC101.19 has become unusually accessible to V3 Abs. Berro2009 (neutralization, binding affinity)
19b: This review summarizes 19b Ab epitope, properties and neutralization activity. Kramer2007 (review)
19b: Similarity level of the 19b binding site pentapeptide -I----G--FY-T to the host proteome was low, with the low-similarity 5-mer occurring in the host proteome 4 times, indicating that this peptide can be used to elicit Abs for active/passive immunotherapy with low risk of cross-reaction with the host proteome. Kanduc2008
19b: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. 19b belonged to the group 1 MAbs, which are able to bind both subtype B and C gp120 proteins and peptides. 19b bound to B gp120 and C gp120 with low avidity. Furthermore, 19b was able to bind both subtype C V3 in the subtype B Env backbone chimera, and reverse, indicating that 19b binds to V3 in a way that is not affected by the gp120 backbone. For subtype B, changes in the position 13 (H13R) and/or position 18 (R18Q) showed no difference of 19b binding compared to wildtype. For subtype C, H13 residue enhanced binding of 19b, but the R18 mutation reduced binding, indicating that R18 affects the conformation of V3 subtype C. Although 19b bound to JR-FL V3, this isolate was resistant to neutralization by 19b, as was SF162. However, a chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by 19b, suggesting an important role of one or more of the three V3 amino acids that differ between these two isolates in defining the epitope and/or structure of the protein. Patel2008 (neutralization, binding affinity, subtype comparisons)
19b: 19b neutralized two of the 15 subtype B isolates tested, 5768-p27 and 92BR020c. Binding affinity of MAb 19b to gp120 was strongly reduced (>10-fold) upon substitutions of Arg304, Ile307, Pro313, Arg315, Phe317, or Tyr318 to Ala. The affinity was moderately reduced (˜4-fold) upon substitution of Lys305. Thr320 was not important for 19b binding. Substituting Asp325 with Ala increased the binding affinity of 19b by 2-fold, suggesting that Ala at this position prevents formation of a salt bridge thus allowing for a better presentation of 19b epitope. 19b neutralized 5768-p27 more potently than 92BR020c although the viruses have same V3 residues important for 19b binding. 5768-p27 has a Met at position 309 and 92BR020c has Ile, indicating that 19b requires an aliphatic side chain at position 309. The inability of 19b to neutralize 6 of the 15 viruses tested could be explained by substitutions at important contact residues, while its inability to neutralize the remaining 6 viruses could not be explained by this. The fine specificity of 19b was mapped onto V3 in the structural context of gp120. Binding site was formed by Arg304 in the N-terminal V3 stem, and Arg315, Phe317, and Tyr318 were in the C-terminal half of the V3 tip. The presence of Pro313 and Arg315 is required to form the V3 tip hairpin turn and juxtapose the true contact residues. Thus, 19b may need to interact with V3 from an angle, which does not permit access to V3 on many different primary viruses. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
19b: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 19b and other MAbs. Gao2007 (antibody binding site, review)
19b: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown to bind with relatively high avidity. Sheppard2007a (variant cross-reactivity)
19b: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed. Srivastava2005 (neutralization, variant cross-reactivity, review, subtype comparisons)
19b: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1. McCann2005 (antibody binding site, review)
19b: This Ab was shown to infrequently neutralize cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors with and without broadly cross-reactive neutralizing antibodies. Cham2006 (neutralization, variant cross-reactivity, subtype comparisons)
19b: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. 19b was shown to bind specifically to all the recombinant proteins as well as to the gp120 from two subtype B isolates. The specific binding of his Ab to CON-S indicated that its conformational epitope was intact. Liao2006 (antibody binding site, vaccine antigen design, subtype comparisons)
19b: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO. Selvarajah2005 (vaccine antigen design, vaccine-induced immune responses)
19b: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset also neutralize some primary isolates. Gorny2003 (review)
19b: This paper attempts to engineer a gp120 molecule that would focus the immune response onto the IgG1b12 epitope. Adding a glycosylation sequon (P313N) to the V3 loop knocked out binding to anti-V3 MAbs loop 2, 19b and 447-52-D. Pantophlet2003b (vaccine antigen design)
19b: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the V3 MAbs used. Zwick2003a (antibody interactions)
19b: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-2999) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs. Kwong2002 (antibody binding site)
19b: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- while b12 was potent at neutralizing the three primary virions JR-CSF, A DA, and 89.6, the Abs F105, 19b, and Fab b6 were overall very poor neutralizers. Poignard2003
19b: A rare mutation in the neutralization sensitive R2-strain in the proximal limb of the V3 region caused Env to become sensitive to neutralization by MAbs directed against the CD4 binding site (CD4BS), CD4-induced (CD4i) epitopes, soluble CD4 (sCD4), and HNS2, a broadly neutralizing sera -- 2/12 anti-V3 MAbs tested (19b and 694/98-D) neutralized R2, as did 2/3 anti-CD4BS MAbs (15e and IgG1b12), 2/2 CD4i MAbs (17b and 4.8D), and 2G12 and 2F5 -- thus multiple epitopes on R2 are functional targets for neutralization and the neutralization sensitivity profile of R2 is intermediate between the highly sensitive MN-TCLA strain and the typically resistant MN-primary strain. Zhang2002
19b: Ab binding characteristics of SOS gp140 were tested using SPR and RIPA -- SOS gp140 is gp120-gp41 bound by a disulfide bond -- NAbs 2G12, 2F5, IgG1b12, CD4 inducible 17b, and 19b bound to SOS gp140 better than uncleaved gp140 (gp140unc) and gp120 -- non-neutralizing MAbs 2.2B (binds to gp41 in gp140unc) and 23A (binds gp120) did not bind SOS gp140. Schulke2002
19b: Mutations in two glycosylation sites in the V2 region of HIV-1 ADA at positions 190 and 197 (187 DNTSYRLINCNTS 199) cause the virus to become CD4-independent and able to enter cells through CCR5 alone -- these same mutations tended to increase the neutralization sensitivity of the virus, including to 19b. Kolchinsky2001
19b: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form but 19b was an exception and required around 950 ng/ml to neutralize either form. Park2000
19b: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes. Binley2000
19b: No detectable neutralizing activity among primary isolates with different co-receptor usage -- some neutralization of TCLA strains. Trkola1998
19b: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope. Parren1998
19b: Used as a control in this Hx10 binding and neutralizing MAb study because 19b does not bind to Hx10. Mondor1998
19b: Neutralizes TCLA strains but not primary isolates. Parren1997
19b: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- 19b has an epitope involving the tip of the V3 loop, with 5 or 6 essential amino acids distributed within a 12 amino acid stretch -- the previously determined binding site was confirmed -I----G--FY-T and some tolerated variants described, the I can be I, V, or L, the Y can be Y, F, or W -- probably a beta-turn is required for FY or FF binding, but WY can bind without the context of the turn. Boots1997
19b: Viral binding inhibition by 19b was weakly correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5) Ugolini1997
19b: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 19b bound monomer, did not bind oligomer or neutralize JRFL. Fouts1997
19b: In a multilaboratory blinded study, failed to consistently neutralize any of nine B clade primary isolates -- there were four sequences with variations in the defined epitope among the 9 isolates tested. DSouza1997
19b: Inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study. Trkola1996b
19b: MIP-1alpha binding to CCR-5 expressing cells can be inhibited by gp120-sCD4 -- binding of 19b blocks this inhibition. Wu1996
19b: Not as effective as IgG1b12 at neutralization ex vivo of virus direct from plasma of HIV-1 infected individuals. Gauduin1996
19b: Review: more broadly cross-reactive than anti-V3 tip MAb 447-D. Moore1995c
19b: Despite broad gp120 binding reactivity, not broadly neutralizing. Moore1995b
19b: Binds to gp120 epitopes from clades A,B,C,E, and F -- weakly neutralized some B and one C clade virus. Epitope is -I----G--FY-T with invariant contacts reported while variable residues are signified by dashes. Consensus sequences for each clade are as follows, where the underlined residues contribute to Ab 19b binding: SVHIGPGQAFYAT (Clade A), SIHIGPGRAFYTT (Clade B), SIRIGPGQTFYAT (Clade C), RTHIGPQALYT T (Clade D), SITIGPGQVFYRT (Clade E), SIHIGPGQAFYAT (Clade F). Author reported HXB2 numbering is gp160(309-320). Moore1995a (antibody binding site, optimal epitope, novel epitope)
19b: Formalin inactivation of virus at 0.1% formalin for 10 hours at 4 degrees was optimal for inactivation of virus while maintaining epitope integrity. Sattentau1995
19b: Competition studies with human sera from seroconverting individuals showed that anti-CD4 BS antibodies can arise very early in infection, comparable or prior to anti-V3 antibodies. Moore1994d
19b: V3 loop binding MAb that is more broadly clade cross-reactive than most (binds to 19/29 clade B and 10/12 clade E gp120s). Novel, optimal epitope is reported as -I----G--FY-T. While several changes are tolerated, the following are inhibitory -I---PG--FY-T, -S---RG--YH-T, -I----G--LV-T, -I----G--FL-T. Moore1994b (optimal epitope, novel epitope)

References

Showing 65 of 65 references.

Isolation Paper
Robinson1990c J. E. Robinson, D. Holton, S. Pacheco-Morell, J. Liu, and H. McMurdo. Identification of Conserved and Variable Epitopes of Human Immunodeficiency Virus Type-1 (HIV-1) gp120 by Human Monoclonal Antibodies Produced by EBV Transformed Cell Lines. AIDS Res. Hum. Retroviruses, 6:567-579, 1990. PubMed ID: 1694449. Show all entries for this paper.

Berro2009 Reem Berro, Rogier W. Sanders, Min Lu, Per J. Klasse, and John P. Moore. Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry. PLoS Pathog., 5(8):e1000548, Aug 2009. PubMed ID: 19680536. Show all entries for this paper.

Binley1997 J. M. Binley, H. Arshad, T. R. Fouts, and J. P. Moore. An investigation of the high avidity antibody response to gp120 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 13:1007-1015, 1997. PubMed ID: 9264287. Show all entries for this paper.

Bontjer2010 Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824. Show all entries for this paper.

Boots1997 L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247. Show all entries for this paper.

Bradley2016a Todd Bradley, Ashley Trama, Nancy Tumba, Elin Gray, Xiaozhi Lu, Navid Madani, Fatemeh Jahanbakhsh, Amanda Eaton, Shi-Mao Xia, Robert Parks, Krissey E. Lloyd, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Susan Barnett, Salim S. Abdool-Karim, Scott D. Boyd, Bruno Melillo, Amos B. Smith, 3rd., Joseph Sodroski, Thomas B. Kepler, S. Munir Alam, Feng Gao, Mattia Bonsignori, Hua-Xin Liao, M Anthony Moody, David Montefiori, Sampa Santra, Lynn Morris, and Barton F. Haynes. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity. EBioMedicine, 12:196-207, Oct 2016. PubMed ID: 27612593. Show all entries for this paper.

Castillo-Menendez2019 Luis R. Castillo-Menendez, Hanh T. Nguyen, and Joseph Sodroski. Conformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J. Virol., 93(3), 1 Feb 2019. PubMed ID: 30429345. Show all entries for this paper.

Cham2006 Fatim Cham, Peng Fei Zhang, Leo Heyndrickx, Peter Bouma, Ping Zhong, Herman Katinger, James Robinson, Guido van der Groen, and Gerald V. Quinnan, Jr. Neutralization and Infectivity Characteristics of Envelope Glycoproteins from Human Immunodeficiency Virus Type 1 Infected Donors Whose Sera Exhibit Broadly Cross-Reactive Neutralizing Activity. Virology, 347(1):36-51, 30 Mar 2006. PubMed ID: 16378633. Show all entries for this paper.

Chen2015 Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642. Show all entries for this paper.

Depetris2012 Rafael S Depetris, Jean-Philippe Julien, Reza Khayat, Jeong Hyun Lee, Robert Pejchal, Umesh Katpally, Nicolette Cocco, Milind Kachare, Evan Massi, Kathryn B. David, Albert Cupo, Andre J. Marozsan, William C. Olson, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, and John P Moore. Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers. J. Biol. Chem., 287(29):24239-24254, 13 Jul 2012. PubMed ID: 22645128. Show all entries for this paper.

deTaeye2015 Steven W. de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, Laura K. Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L. Torres, Heather Arendt, Joanne DeStefano, Wayne C. Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C. Montefiori, P. J. Klasse, Kelly K. Lee, John P. Moore, Ian A. Wilson, Andrew B. Ward, and Rogier W. Sanders. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-Neutralizing Epitopes. Cell, 163(7):1702-1715, 17 Dec 2015. PubMed ID: 26687358. Show all entries for this paper.

deTaeye2018 Steven W. de Taeye, Alba Torrents de la Peña, Andrea Vecchione, Enzo Scutigliani, Kwinten Sliepen, Judith A. Burger, Patricia van der Woude, Anna Schorcht, Edith E. Schermer, Marit J. van Gils, Celia C. LaBranche, David C. Montefiori, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the gp120 V3 Loop through Hydrophobic Interactions Reduces the Immunodominant V3-Directed Non-Neutralizing Response to HIV-1 Envelope Trimers. J. Biol. Chem., 293(5):1688-1701, 2 Feb 2018. PubMed ID: 29222332. Show all entries for this paper.

Ding2015 Shilei Ding, Maxime Veillette, Mathieu Coutu, Jérémie Prévost, Louise Scharf, Pamela J. Bjorkman, Guido Ferrari, James E. Robinson, Christina Stürzel, Beatrice H. Hahn, Daniel Sauter, Frank Kirchhoff, George K. Lewis, Marzena Pazgier, and Andrés Finzi. A Highly Conserved Residue of the HIV-1 gp120 Inner Domain Is Important for Antibody-Dependent Cellular Cytotoxicity Responses Mediated by Anti-cluster A Antibodies. J. Virol., 90(4):2127-2134, Feb 2016. PubMed ID: 26637462. Show all entries for this paper.

DSouza1997 M. P. D'Souza, D. Livnat, J. A. Bradac, S. H. Bridges, the AIDS Clinical Trials Group Antibody Selection Working Group, and Collaborating Investigators. Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. J. Infect. Dis., 175:1056-1062, 1997. Five laboratories evaluated neutralization of nine primary B clade isolates by a coded panel of seven human MAbs to HIV-1 subtype B envelope. IgG1b12, 2G12, 2F5 showed potent and broadly cross-reactive neutralizing ability; F105, 447/52-D, 729-D, 19b did not neutralize the primary isolates. PubMed ID: 9129066. Show all entries for this paper.

Fouda2013 Genevieve G. Fouda, Tatenda Mahlokozera, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Gerald Learn, Surender B. Kumar, S. Moses Dennison, Elizabeth Russell, Katherine Rizzolo, Frederick Jaeger, Fangping Cai, Nathan A. Vandergrift, Feng Gao, Beatrice Hahn, George M. Shaw, Christina Ochsenbauer, Ronald Swanstrom, Steve Meshnick, Victor Mwapasa, Linda Kalilani, Susan Fiscus, David Montefiori, Barton Haynes, Jesse Kwiek, S. Munir Alam, and Sallie R. Permar. Postnatally-Transmitted HIV-1 Envelope Variants Have Similar Neutralization-Sensitivity and Function to That of Nontransmitted Breast Milk Variants. Retrovirology, 10:3, 2013. PubMed ID: 23305422. Show all entries for this paper.

Fouts1997 T. R. Fouts, J. M. Binley, A. Trkola, J. E. Robinson, and J. P. Moore. Neutralization of the Human Immunodeficiency Virus Type 1 Primary Isolate JR-FL by Human Monoclonal Antibodies Correlates with Antibody Binding to the Oligomeric Form of the Envelope Glycoprotein Complex. J. Virol., 71:2779-2785, 1997. To test whether antibody neutralization of HIV-1 primary isolates is correlated with the affinities for the oligomeric envelope glycoproteins, JRFL was used as a model primary virus and a panel of 13 human MAbs were evaluated for: half-maximal binding to rec monomeric JRFL gp120; half-maximal binding to oligomeric - JRFL Env expressed on the surface of transfected 293 cells; and neutralization of JRFL in a PBMC-based neutralization assay. Antibody affinity for oligomeric JRFL Env but not monomeric JRFL gp120 correlated with JRFL neutralization. PubMed ID: 9060632. Show all entries for this paper.

Gao2007 Feng Gao, Hua-Xin Liao, Beatrice H. Hahn, Norman L. Letvin, Bette T. Korber, and Barton F. Haynes. Centralized HIV-1 Envelope Immunogens and Neutralizing Antibodies. Curr. HIV Res., 5(6):572-577, Nov 2007. PubMed ID: 18045113. Show all entries for this paper.

Gauduin1996 M.-C. Gauduin, G. P. Allaway, P. J. Maddon, C. F. Barbas III, D. R. Burton, and R. A. Koup. Effective Ex Vivo Neutralization of Human Immunodeficiency Virus Type 1 in Plasma by Recombinant Immunoglobulin Molecules. J. Virol., 70:2586-2592, 1996. Virus direct from plasma from six HIV-1 infected individuals was used for neutralization assay. MAb 19b could neutralize 2/6 plasma samples, while MAb IgG1b12 could neutralize 5/6 plasma samples. CD4-based molecules were also tested: CD4-IgG2 was effective in the it ex vivo assay, but sCD4 was not. Thus, MAbs IgG1b12 and CD4-IgG2 have broad and potent it in vitro and it ex vivo neutralizing activities. PubMed ID: 8642690. Show all entries for this paper.

Gorny2003 Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162. Show all entries for this paper.

Jeffries2016 T. L. Jeffries, Jr., C. R. Sacha, J. Pollara, J. Himes, F. H. Jaeger, S. M. Dennison, E. McGuire, E. Kunz, J. A. Eudailey, A. M. Trama, C. LaBranche, G. G. Fouda, K. Wiehe, D. C. Montefiori, B. F. Haynes, H.-X. Liao, G. Ferrari, S. M. Alam, M. A. Moody, and S. R. Permar. The Function and Affinity Maturation of HIV-1 gp120-Specific Monoclonal Antibodies Derived from Colostral B Cells. Mucosal. Immunol., 9(2):414-427, Mar 2016. PubMed ID: 26242599. Show all entries for this paper.

Johnson2017 Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B. Smith, III, Navid Madani, Joseph Sodroski, and Hillel Haim. Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States. J. Virol., 91(15), 1 Aug 2017. PubMed ID: 28490588. Show all entries for this paper.

Joubert2010 Marisa K. Joubert, Nichole Kinsley, Alexio Capovilla, B. Trevor Sewell, Mohamed A. Jaffer, and Makobetsa Khati. A Modeled Structure of an Aptamer-gp120 Complex Provides Insight into the Mechanism of HIV-1 Neutralization. Biochemistry, 49(28):5880-5890, 20 Jul 2010. PubMed ID: 20527993. Show all entries for this paper.

Julien2015 Jean-Philippe Julien, Jeong Hyun Lee, Gabriel Ozorowski, Yuanzi Hua, Alba Torrents de la Peña, Steven W. de Taeye, Travis Nieusma, Albert Cupo, Anila Yasmeen, Michael Golabek, Pavel Pugach, P. J. Klasse, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Design and Structure of Two HIV-1 Clade C SOSIP.664 Trimers That Increase the Arsenal of Native-Like Env Immunogens. Proc. Natl. Acad. Sci. U.S.A., 112(38):11947-11952, 22 Sep 2015. PubMed ID: 26372963. Show all entries for this paper.

Kanduc2008 Darja Kanduc, Rosario Serpico, Alberta Lucchese, and Yehuda Shoenfeld. Correlating Low-Similarity Peptide Sequences and HIV B-Cell Epitopes. Autoimmun. Rev., 7(4):291-296, Feb 2008. PubMed ID: 18295732. Show all entries for this paper.

Kolchinsky2001 P. Kolchinsky, E. Kiprilov, P. Bartley, R. Rubinstein, and J. Sodroski. Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J. Virol., 75(7):3435--43, Apr 2001. URL: http://jvi.asm.org/cgi/content/full/75/7/3435. PubMed ID: 11238869. Show all entries for this paper.

Kramer2007 Victor G. Kramer, Nagadenahalli B. Siddappa, and Ruth M. Ruprecht. Passive Immunization as Tool to Identify Protective HIV-1 Env Epitopes. Curr. HIV Res., 5(6):642-55, Nov 2007. PubMed ID: 18045119. Show all entries for this paper.

Kwong2002 Peter D. Kwong, Michael L. Doyle, David J. Casper, Claudia Cicala, Stephanie A. Leavitt, Shahzad Majeed, Tavis D. Steenbeke, Miro Venturi, Irwin Chaiken, Michael Fung, Hermann Katinger, Paul W. I. H. Parren, James Robinson, Donald Van Ryk, Liping Wang, Dennis R. Burton, Ernesto Freire, Richard Wyatt, Joseph Sodroski, Wayne A. Hendrickson, and James Arthos. HIV-1 Evades Antibody-Mediated Neutralization through Conformational Masking of Receptor-Binding Sites. Nature, 420(6916):678-682, 12 Dec 2002. Comment in Nature. 2002 Dec 12;420(6916):623-4. PubMed ID: 12478295. Show all entries for this paper.

Liao2006 Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred McAdams, Eric A. Weaver, Zenaido Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, and Barton F. Haynes. A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets of Subtype B and C HIV-1 Primary Viruses. Virology, 353(2):268-282, 30 Sep 2006. PubMed ID: 17039602. Show all entries for this paper.

Liu2015a Mengfei Liu, Guang Yang, Kevin Wiehe, Nathan I. Nicely, Nathan A. Vandergrift, Wes Rountree, Mattia Bonsignori, S. Munir Alam, Jingyun Gao, Barton F. Haynes, and Garnett Kelsoe. Polyreactivity and Autoreactivity among HIV-1 Antibodies. J. Virol., 89(1):784-798, Jan 2015. PubMed ID: 25355869. Show all entries for this paper.

McCann2005 C. M. Mc Cann, R. J. Song, and R. M. Ruprecht. Antibodies: Can They Protect Against HIV Infection? Curr. Drug Targets Infect. Disord., 5(2):95-111, Jun 2005. PubMed ID: 15975016. Show all entries for this paper.

Mondor1998 I. Mondor, S. Ugolini, and Q. J. Sattentau. Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and Gp120 Dependent and Requires Cell Surface Heparans. J. Virol., 72:3623-3634, 1998. PubMed ID: 9557643. Show all entries for this paper.

Moore1994d J. P. Moore, Y. Cao, D. D. Ho, and R. A. Koup. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J. Virol., 68:5142-5155, 1994. Three seroconverting individuals were studied. The earliest detectable anti-gp120 antibodies were both conformational and anti-V3 loop, and could be detected only after the peak viremia has passed. No uniform pattern of autologous neutralizing anti-CD4BS or anti-V3 MAbs was observed. PubMed ID: 8035514. Show all entries for this paper.

Moore1995a J. P. Moore, A. Trkola, B. Korber, L. J. Boots, J. A. Kessler II, F. E. McCutchan, J. Mascola, D. D. Ho, J. Robinson, and A. J. Conley. A Human Monoclonal Antibody to a Complex Epitope in the V3 Region of gp120 of Human Immunodeficiency Virus Type 1 Has Broad Reactivity within and outside Clade B. J. Virol., 69:122-130, 1995. The epitope was defined as including amino acids on both sides of the loop of the V3 loop: -I----G--FY-T, where the G is the second G of the GPGR tip of the loop. This antibody bound well to gp120 molecules from clades A,B,C,E, and F, when the critical amino acids were present. Binding did not parallel neutralization however; 19b could produce a 50-fold reduction of infectivity in some primary B isolates, and in C clade isolates at low virus input concentrations, but not in isolates from all clades where binding could occur (A,E, and F). PubMed ID: 7527082. Show all entries for this paper.

Moore1995b J. P. Moore, Y. Cao, L. Qing, Q. J. Sattentau, J. Pyati, R. Koduri, J. Robinson, C. F. Barbas III, D. R. Burton, and D. D. Ho. Primary Isolates of Human Immunodeficiency Virus Type I Are Relatively Resistant to Neutralization by Monoclonal Antibodies to gp120, and Their Neutralization Is Not Predicted by Studies with Monomeric gp120. J. Virol., 69:101-109, 1995. A panel of anti-gp120 MAbs and sera from HIV-1 infected individuals was tested for its ability to neutralize primary isolates. Most MAbs bound with high affinity to gp120 monomers from the various isolates, but were not effective at neutralizing. The MAb IgG1b12, which binds to a discontinuous anti-CD4 binding site epitope, was able to neutralize most of the primary isolates. PubMed ID: 7527081. Show all entries for this paper.

Moore1995c J. P. Moore and D. D. Ho. HIV-1 Neutralization: The Consequences of Adaptation to Growth on Transformed T-Cells. AIDS, 9(suppl A):S117-S136, 1995. This review considers the relative importance of a neutralizing antibody response for the development of a vaccine, and for disease progression during the chronic phase of HIV-1 infection. It suggests that T-cell immunity may be more important. The distinction between MAbs that can neutralize primary isolates, and those that are effective at neutralizing only laboratory adapted strains is discussed in detail. Alternative conformations of envelope and non-contiguous interacting domains in gp120 are discussed. The suggestion that soluble monomeric gp120 may serve as a viral decoy that diverts the humoral immune response it in vivo is put forth. PubMed ID: 8819579. Show all entries for this paper.

Pantophlet2003b Ralph Pantophlet, Ian A. Wilson, and Dennis R. Burton. Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol., 77(10):5889-8901, May 2003. PubMed ID: 12719582. Show all entries for this paper.

Parren1997 P. W. Parren, M. C. Gauduin, R. A. Koup, P. Poignard, Q. J. Sattentau, P. Fisicaro, and D. R. Burton. Erratum to Relevance of the Antibody Response against Human Immunodeficiency Virus Type 1 Envelope to Vaccine Design. Immunol. Lett., 58:125-132, 1997. corrected and republished article originally printed in Immunol. Lett. 1997 Jun;57(1-3):105-112. PubMed ID: 9271324. Show all entries for this paper.

Parren1998 P. W. Parren, I. Mondor, D. Naniche, H. J. Ditzel, P. J. Klasse, D. R. Burton, and Q. J. Sattentau. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol., 72:3512-9, 1998. The authors propose that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Neutralization was assayed T-cell-line-adapted HIV-1 isolates. Binding of Fabs to monomeric rgp120 was not correlated with binding to functional oligomeric gp120 or neutralization, while binding to functional oligomeric gp120 was highly correlated with neutralization. The ratios of oligomer binding/neutralization were similar for antibodies to different neutralization epitopes, with a few exceptions. PubMed ID: 9557629. Show all entries for this paper.

Patel2008 Milloni B Patel, Noah G. Hoffman, and Ronald Swanstrom. Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins. J. Virol., 82(2):903-916, Jan 2008. PubMed ID: 18003735. Show all entries for this paper.

Poignard2003 Pascal Poignard, Maxime Moulard, Edwin Golez, Veronique Vivona, Michael Franti, Sara Venturini, Meng Wang, Paul W. H. I. Parren, and Dennis R. Burton. Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol., 77(1):353-365, Jan 2003. PubMed ID: 12477840. Show all entries for this paper.

Prevost2018 Jérémie Prévost, Jonathan Richard, Shilei Ding, Beatriz Pacheco, Roxanne Charlebois, Beatrice H Hahn, Daniel E Kaufmann, and Andrés Finzi. Envelope Glycoproteins Sampling States 2/3 Are Susceptible to ADCC by Sera from HIV-1-Infected Individuals. Virology, 515:38-45, Feb 2018. PubMed ID: 29248757. Show all entries for this paper.

Pugach2015 Pavel Pugach, Gabriel Ozorowski, Albert Cupo, Rajesh Ringe, Anila Yasmeen, Natalia de Val, Ronald Derking, Helen J. Kim, Jacob Korzun, Michael Golabek, Kevin de Los Reyes, Thomas J. Ketas, Jean-Philippe Julien, Dennis R. Burton, Ian A. Wilson, Rogier W. Sanders, P. J. Klasse, Andrew B. Ward, and John P. Moore. A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene. J. Virol., 89(6):3380-3395, Mar 2015. PubMed ID: 25589637. Show all entries for this paper.

Robinson1992 J. Robinson, H. Yoshiyama, D. Holton, S. Elliot, and D.D. Ho. Distinct Antigenic Sites on HIV gp120 Identified by a Panel of Human Monoclonal Antibodies. J. Cell Biochem., Suppl 16E:71, 1992. Show all entries for this paper.

Sanders2013 Rogier W. Sanders, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Anila Yasmeen, Natalia de Val, Helen J. Kim, Claudia Blattner, Alba Torrents de la Peña, Jacob Korzun, Michael Golabek, Kevin de los Reyes, Thomas J. Ketas, Marit J. van Gils, C. Richter King, Ian A. Wilson, Andrew B. Ward, P. J. Klasse, and John P. Moore. A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but not Non-Neutralizing Antibodies. PLoS Pathog., 9(9):e1003618, Sep 2013. PubMed ID: 24068931. Show all entries for this paper.

Sattentau1995 Q. J. Sattentau, S. Zolla-Pazner, and P. Poignard. Epitope Exposure on Functional, Oligomeric HIV-1 gp41 Molecules. Virology, 206:713-717, 1995. Most gp41 epitopes are masked when associated with gp120 on the cell surface. Weak binding of anti-gp41 MAbs can be enhanced by treatment with sCD4. MAb 2F5 binds to a membrane proximal epitope which binds in the presence of gp120 without sCD4. PubMed ID: 7530400. Show all entries for this paper.

Sattentau1995b Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064. Show all entries for this paper.

Schiffner2016 Torben Schiffner, Natalia de Val, Rebecca A. Russell, Steven W. de Taeye, Alba Torrents de la Peña, Gabriel Ozorowski, Helen J. Kim, Travis Nieusma, Florian Brod, Albert Cupo, Rogier W. Sanders, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens. J. Virol., 90(2):813-828, 28 Oct 2015. PubMed ID: 26512083. Show all entries for this paper.

Schiffner2018 Torben Schiffner, Jesper Pallesen, Rebecca A. Russell, Jonathan Dodd, Natalia de Val, Celia C. LaBranche, David Montefiori, Georgia D. Tomaras, Xiaoying Shen, Scarlett L. Harris, Amin E. Moghaddam, Oleksandr Kalyuzhniy, Rogier W. Sanders, Laura E. McCoy, John P. Moore, Andrew B. Ward, and Quentin J. Sattentau. Structural and Immunologic Correlates of Chemically Stabilized HIV-1 Envelope Glycoproteins. PLoS Pathog., 14(5):e1006986, May 2018. PubMed ID: 29746590. Show all entries for this paper.

Schulke2002 Norbert Schulke, Mika S. Vesanen, Rogier W. Sanders, Ping Zhu, Min Lu, Deborah J. Anselma, Anthony R. Villa, Paul W. H. I. Parren, James M. Binley, Kenneth H. Roux, Paul J. Maddon, John P. Moore, and William C. Olson. Oligomeric and Conformational Properties of a Proteolytically Mature, Disulfide-Stabilized Human Immunodeficiency Virus Type 1 gp140 Envelope Glycoprotein. J. Virol., 76(15):7760-76, Aug 2002. PubMed ID: 12097589. Show all entries for this paper.

Scott1990 C. F. Scott, Jr., S. Silver, A. T. Profy, S. D. Putney, A. Langlois, K. Weinhold, and J. E. Robinson. Human Monoclonal Antibody That Recognizes the V3 Region of Human Immunodeficiency Virus gp120 and Neutralizes the Human T-Lymphotropic Virus Type IIIMN Strain. Proc. Natl. Acad. Sci. U.S.A., 87:8597-8601, 1990. PubMed ID: 1700435. Show all entries for this paper.

Selvarajah2005 Suganya Selvarajah, Bridget Puffer, Ralph Pantophlet, Mansun Law, Robert W. Doms, and Dennis R. Burton. Comparing Antigenicity and Immunogenicity of Engineered gp120. J. Virol., 79(19):12148-12163, Oct 2005. PubMed ID: 16160142. Show all entries for this paper.

Sheppard2007a Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037. Show all entries for this paper.

Srivastava2005 Indresh K. Srivastava, Jeffrey B. Ulmer, and Susan W. Barnett. Role of Neutralizing Antibodies in Protective Immunity Against HIV. Hum. Vaccin., 1(2):45-60, Mar-Apr 2005. PubMed ID: 17038830. Show all entries for this paper.

Trkola1996b A. Trkola, T. Dragic, J. Arthos, J. M. Binley, W. C. Olson, G. P. Allaway, C. Cheng-Mayer, J. Robinson, P. J. Maddon, and J. P. Moore. CD4-Dependent, Antibody-Sensitive Interactions between HIV-1 and Its Co-Receptor CCR-5. Nature, 384:184-187, 1996. CCR-5 is a co-factor for fusion of HIV-1 strains of the non-syncytium-inducing (NSI) phenotype with CD4+ T-cells. CD4 binding greatly increases the efficiency of gp120-CCR-5 interaction. Neutralizing MAbs against the V3 loop and CD4-induced epitopes on gp120 inhibited the interaction of gp120 with CCR-5, without affecting gp120-CD4 binding. PubMed ID: 8906796. Show all entries for this paper.

Trkola1998 A. Trkola, T. Ketas, V. N. Kewalramani, F. Endorf, J. M. Binley, H. Katinger, J. Robinson, D. R. Littman, and J. P. Moore. Neutralization Sensitivity of Human Immunodeficiency Virus Type 1 Primary Isolates to Antibodies and CD4-Based Reagents Is Independent of Coreceptor Usage. J. Virol., 72:1876-1885, 1998. PubMed ID: 9499039. Show all entries for this paper.

Ugolini1997 S. Ugolini, I. Mondor, P. W. H. I Parren, D. R. Burton, S. A. Tilley, P. J. Klasse, and Q. J. Sattentau. Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line-Adapted HIV-1 Neutralization. J. Exp. Med., 186:1287-1298, 1997. PubMed ID: 9334368. Show all entries for this paper.

Witt2017 Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945. Show all entries for this paper.

Wu1996 L. Wu, N. P. Gerard, R. Wyatt, H. Choe, C. Parolin, N. Ruffing, A. Borsetti, A. A. Cardoso, E. Desjardin, W. Newman, C. Gerard, and J. Sodroski. CD4-Induced Interaction of Primary HIV-1 gp120 Glycoproteins with the Chemokine Receptor CCR-5. Nature, 384:179-183, 1996. Results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. CD4-induced or V3 neutralizing MAbs block the interaction of gp120-CD4 complexes with CCR-5. PubMed ID: 8906795. Show all entries for this paper.

Yasmeen2014 Anila Yasmeen, Rajesh Ringe, Ronald Derking, Albert Cupo, Jean-Philippe Julien, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, John P. Moore, and Per Johan Klasse. Differential Binding of Neutralizing and Non-Neutralizing Antibodies to Native-Like Soluble HIV-1 Env Trimers, Uncleaved Env Proteins, and Monomeric Subunits. Retrovirology, 11:41, 2014. PubMed ID: 24884783. Show all entries for this paper.

Zwick2003a Michael B. Zwick, Robert Kelleher, Richard Jensen, Aran F. Labrijn, Meng Wang, Gerald V. Quinnan, Jr., Paul W. H. I. Parren, and Dennis R. Burton. A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12. J. Virol., 77(12):6965-6978, Jun 2003. PubMed ID: 12768015. Show all entries for this paper.

Displaying record number 504

Download this epitope record as JSON.

MAb ID	58.2
HXB2 Location	gp160(310-317) DNA(7152..7175)	gp160 Epitope Map
Author Location	gp120( MN)
Research Contact	Repligen Corp.
Epitope	`HIGPGRAF`	Epitope Alignment
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L
Species (Isotype)	mouse(IgG1κ)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, neutralization, review, structure, subtype comparisons, variant cross-reactivity

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade MN
Vaccine component	Env V3

Notes

Showing 12 of 12 notes.

58.2: 58.2 complexed with sCD4 and both parental and GnTI virus (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps). Binley2010
58.2: Data is summarized on the X-ray crystal structures resolution and NMR studies of 58.2. Sirois2007 (review, structure)
58.2: 58.2 neutralized 5 of the 15 subtype B isolates tested, of which 4 were resistant to neutralization by MAbs 19b, 39F, CO11, F2A3, F530, LA21 and LE311. Angle of interaction between 58.2 and V3 was shown by superimposing the Fab fragment of the Ab with V3. 58.2 was shown to interact with V3 from a nearly identical angle as MAb 447D. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, structure)
58.2: The crystal structure of V3-reactive antibody-peptide complexes were examined. 58.2 completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
58.2: This review summarizes data on crystallographic structures of 58.2 binding to its V3 peptide antigens. Stanfield2005 (antibody binding site, review, structure)
58.2: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. 58.2 could only neutralize B subtype viruses, and seemed to have a minimal epitope of (H/T)IGPGR(A/T)(F/L). Binley2004 (variant cross-reactivity, subtype comparisons)
58.2: 58.2's epitope was noted to be IGPGRAF -- Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding. York2001
58.2: The crystal structure of Fab 58.2 bound to V3 loop peptides was obtained -- conformational changes in the tip of the V3 loop (GPGR) were observed when different MAbs were bound -- 58.2's epitope was defined as KRKRIHIGPGRAFY. Stanfield1999
58.2: Competition ELISAs with serial deletions produced longer estimates of epitope length, RIHIGPGRAFY, than Alanine substitution, suggesting significance of non-contact residues. Seligman1996
58.2: Modest cross-reactivity among B clade gp120s, little outside B clade -- core epitope as I-IHIG. Moore1994b
58.2: Did not synergistically neutralize MN in combination with MAb F105 -- there was synergistic neutralization when combined with sCD4. Potts1993
58.2: Epitope defined by peptide reactivity and changes in affinity with amino acid substitutions -- 4/7 primarily isolates were neutralized. WhiteScharf1993 (antibody generation)

References

Showing 12 of 12 references.

Binley2004 James M. Binley, Terri Wrin, Bette Korber, Michael B. Zwick, Meng Wang, Colombe Chappey, Gabriela Stiegler, Renate Kunert, Susan Zolla-Pazner, Hermann Katinger, Christos J. Petropoulos, and Dennis R. Burton. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. J. Virol., 78(23):13232-13252, Dec 2004. PubMed ID: 15542675. Show all entries for this paper.

Binley2010 James M Binley, Yih-En Andrew Ban, Emma T. Crooks, Dirk Eggink, Keiko Osawa, William R. Schief, and Rogier W. Sanders. Role of Complex Carbohydrates in Human Immunodeficiency Virus Type 1 Infection and Resistance to Antibody Neutralization. J. Virol., 84(11):5637-5655, Jun 2010. PubMed ID: 20335257. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

Displaying record number 500

Download this epitope record as JSON.

MAb ID	447-52D (447/52-DII, 447-52-D, 447d, 447-52-D, 447-D, 447, 447D, 447D-52)
HXB2 Location	gp160(312-315) DNA(7158..7169)	gp160 Epitope Map
Author Location	gp120( MN)
Research Contact	Dr. Susan Zolla-Pazner, NYU Med Center NY, NY; Veteran Affairs Med Center NY, NY; or Cellular Products Inc, Buffalo, NY,
Epitope	`GPGR`	Epitope Alignment
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG3λ)
Patient
Immunogen	HIV-1 infection
Keywords	acute/early infection, ADCC, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, co-receptor, complement, computational epitope prediction, dendritic cells, dynamics, elite controllers, enhancing activity, escape, genital and mucosal immunity, glycosylation, HIV-2, kinetics, mimics, mimotopes, neutralization, optimal epitope, polyclonal antibodies, review, SIV, structure, subtype comparisons, supervised treatment interruptions (STI), Th2, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity, viral fitness and reversion

Notes

Showing 219 of 219 notes.

447-52d: An R5 virus isolated from chronic patient NAB01 (Patient Record# 4723) was adapted in culture to growth in the presence of target cells expressing reduced levels of CD4. Entry kinetics of the virus were altered, and these alterations resulted in extended exposure of CD4-induced neutralization-sensitive epitopes to CD4. Adapted and control viruses were assayed for their neutralization by a panel of neutralizing antibodies targeting several different regions of Env (PGT121, PGT128, 1-79, 447-52d, b6, b12, VRC01, 17b, 4E10, 2F5, Z13e1). Adapted viruses showed greater sensitivity to antibodies targeting the CD4 binding site and the V3 loop. This evolution of Env resulted in increased CD4 affinity but decreased viral fitness, a phenomenon seen also in the immune-privileged CNS, particularly in macrophages. Beauparlant2017 (neutralization, viral fitness and reversion, dynamics, kinetics)
447-52D: Three vaccine regimens administered in guinea pigs over 200 weeks were compared for ability to elicit NAb polyclonal sera. While tier 1 NAb responses did increase with vaccination, tier 2 NAb heterologous responses did not. The 3 regimens were C97 (monovalent, Clade C gp140), 4C (tetravalent, 4 Clade C mosaic gp140s), ABCM (tetravalent, Clades A, B, C and mosaic gp140s). Polyclonal sera generated from the 4C regimen, compared to the C97 regimen, was markedly superior at outcompeting 447-52D binding to gp140 antigens, suggesting that the 4C regimen induced the most robust V3-specific antibodies. Bricault2018 (antibody generation, vaccine-induced immune responses, polyclonal antibodies)
447-52D: The authors mutated two conserved tyrosine (Y) residues within the V2 loop of gp120 Y177 and Y173, individually or in combination, by replacing them with either phenylalanine (F) or alanine (A) in a clade B, tier 1B HIV-1 Env protein (BaL), and in a number of tier 2 HIV-1 Envs from different clades, namely, BG505 (clade A), JR-FL and JR-CSF (clade B), and CM244 (clade E). A consistent hierarchy of neutralization sensitivity was seen among the mutants, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The double-alanine mutation in mutant HIV-1 BaL, Y173A Y177A, increased sensitivity to all the weakly neutralizing MAbs tested and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site, such as F105, 654-30D, and b13. When tested against bNAbs instead, there was a trend to decrease neutralization sensitivity compared to WT, with the exception of N6, PGT151, 10E8, and 2G12, for which there was no change, and of 2F5 and 4E10, which were more effective against the mutant compared to the WT. Guzzo2018 (antibody binding site, binding affinity)
447-52D: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q). Yates2018 (vaccine antigen design, vaccine-induced immune responses, binding affinity)
447-52D: A systems glycobiology approach was applied to reverse engineer the relationship between bNAb binding and glycan effects on Env proteins. Glycan occupancy was interrogated across every potential N-glycan site in 94 recombinant gp120 antigens. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity. The novel synthesized antigens uccessfully bound to target bNAbs with enhanced and selective antigenicity. Yu2018 (glycosylation, vaccine antigen design)
447-52D: The immunologic effects of mutations in the Env cytoplasmic tail (CT) that included increased surface expression were explored using a vaccinia prime/protein boost protocol in mice. After vaccinia primes, CT- modified Envs induced up to 7-fold higher gp120-specific IgG, and after gp120 protein boosts, they elicited up to 16-fold greater Tier-1 HIV-1 neutralizing antibody titers. Envs with or without the TM1 mutations were expressed in HEK 293T cells and analyzed for the relative expression of Ab epitopes including V3 loop crown for 447-52D. Hogan2018 (vaccine antigen design)
447-52D: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. With S306L plus R308L substitutions 447-52D did not bind to SOSIP.v5.2 and SOSIP.v5.2 constructs. deTaeye2018 (broad neutralizer)
447-52D: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens. Johnson2017 (vaccine antigen design)
447-52D: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs (including 447-52D), regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074). Cai2017 (neutralization)
447-52D: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41_ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC₅₀ >50µg/ml). Pugach2015
447-52D: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 447-52D did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either. Sanders2013 (assay or method development, neutralization, binding affinity)
447-52D: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
447D: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. The V3 MAbs tested were: 447, 2219, and 2557. Upadhyay2014 (glycosylation, neutralization)
447-52D: A computational method, MDE, predicts the presence of neutralization epitopes in the V3 loop solely from the viral sequence and the crystal structure of the antibody. For V3-specific mAbs 2219 and 447-52D, the method accurately predicted the presence of neutralization epitopes in diverse strains of HIV-1. Identification of Ab-targeted neutralization epitopes in silico enables easy prediction of the reactivity of specific mAbs across diverse variants, and facilitates rational design of immunogens. Shmelkov2014 (computational epitope prediction)
447-52D: This study proposes a mimotope model of the V3 crown epitope in which the PR-L and GPG sequences represent the two known epitope binding sites. Rabbit serum to these mimotopes recognized the V3 peptides and moderately decreased the fusion between HIV-1 Env- and CD4-expressing Jurkat cells. MAb 447-52D has been used as V3 epitope core recognizing Ab. The most intriguing characteristic of this mimotope model of the V3 epitope is the absence of the arginine at the position next to the GPG, which offers the flexibility of this phage-displayed linear peptide affecting the correct interaction between the epitope and the antibody tolerating substitutions of the GPG amino acids. Gazarian2013 (mimotopes)
447-52D: Study evaluated 4 gp140 Env protein vaccine immunogens derived from an elite neutralizer donor VC10042, an HIV+ African American male from Vanderbilt cohort. Env immunogens, VC10042.05, VC10042.05RM, VC10042.08 and VC10042.ela, elicited high titers of cross-reactive Abs recognizing V1/V2 regions. 447-52D bound to all 4 trimeric Env. Carbonetti2014 (elite controllers, vaccine-induced immune responses)
447-52D: This study showed that the inability of Env to elicit the production of broadly neutralizing Abs is due to the inability of diverse Env to engage the germ line B cell receptor forms of known bNAbs. 447-52D bound to all the Envs tested except the clade B REJO, the consensus A1 sequence, the clade 405c, and the clade A/E A244. The predicted germ line version of 447-52D did not exhibit any detectable binding against these Envs. Ca²⁺ influx through the 447-52D BCR was also tested as a function of binding affinity. Removal of selected N-linked glycosylaion sites on Env did not confer binding to the predicted germline 447-52D. McGuire2014 (antibody interactions, antibody lineage)
447-52D: Describes the mutagenesis of plasmid P5Q (a scFv antibody derived from mAb 447). Cites the original mAb 447 as first described by Buchbinder et al. 1992. Lewis1995 (binding affinity, antibody sequence)
447-52D: The sera of 20 HIV-1 patients were screened for ADCC in a novel assay measuring granzyme B (GrB) and T cell elimination and reported that complex sera mediated greater levels of ADCC than anti-HIV mAbs. The data suggested that total amount of IgG bound is an important determinant of robust ADCC which improves the vaccine potency. 447-52D was used as an anti-V3 Ab to study effects of Ab specificity and affinity on ADCC against HIV-1 infected targets. Smalls-Mantey2012 (ADCC, assay or method development)
447-52D: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 447-52D had limited neutralizing activity recognizing the V3 loop and carried fewer somatic mutations than bnAbs. Fig S4C described the comparison of Ab framework amino acid replacement vs. interactive surface area on 447-52D. Klein2013 (neutralization, structure, antibody lineage)
447-52D: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. 447-52D was used as a control mAb in the comprehensive set of assays performed. Tomaras2011 (neutralization, polyclonal antibodies)
447-52D: The role of V1V2 in the resistance of HIV-1 to neutralizing Abs was studied using a panel of neutralization-sensitive and -resistant HIV-1 variants and through exchanging regions of Env between neutralization-sensitive and -resistant viruses. An increase in the length of the V1V2 loop and/or the number of potential N-linked glycosylation sites (PNGS) in that same region of Env was directly involved in the neutralization resistance. The introduction of a shorter V1V2 loop from historical seroconverters into the background of Env of HIV-1 from contemporary seroconverters resulted in significant increase in neutralization sensitivity to MAb 447-52D. vanGils2011 (glycosylation, neutralization, escape)
447-52D: The inhibitory activity of HIV-1-specific Abs against HIV-1 replication in langerhans cells (LCs) and interstitial dendritic cells (IDCs) was analyzed. Five well-known NAbs 447-52D, 4E10, b12, 2G12, 2F5 strongly inhibited HIV-1BaL and HIV-1TV1 replication in LCs and IDCs, and their inhibitory activities were stronger than those measured on PBMCs. Inhibition was more efficient by IgGs than corresponding IgAs, due to an Fc receptor-dependent mechanism, where HIV-1 inhibition occurs by binding of the Fc portion of IgGs to Fc receptors. Blocking the binding of the NAb to the FcRs present on the cell surface of the DCs reduced the inhibitory activity of the IgG 447-52D. Finally, nonneutralizing inhibitory action of 447-52D Fab fragments 240D and 246D 246D, which do not exhibit neutralizing activity on PBMCs, reduced the number of HIV-1BaL-infected LCs and IDCs by 90%. Peressin2011 (genital and mucosal immunity, dendritic cells)
447-52D: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities was used to analyze the antigenic integrity of the covalent complexes using capture ELISA. Binding of the cross-linked complex on 447-52D or MN 215 was increased compared with that of gp140 alone. Martin2011 (mimics, binding affinity)
447-52D: Signature motifs specific for neutralization epitopes present in the V3 loop crown were used to determine the presence or absence of MAb-specific epitopes in vaccine immunogens and in break-through viruses infecting vaccine and placebo recipients in the VAX003 and VAX004 Phase III clinical trials. Of the six epitopes present in the immunogens and targeted by known NAbs, only the one targeted by anti-V3 NAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects from VAX003 Thailand cohort compared to the placebo group. The signature motif used for MAb 447-52D is P16, R18 in V3-loop position numbers. Shmelkov2011 (vaccine-induced immune responses)
447-52D: The long-term effect of broadly bNAbs on cell-free HIV particles and their capacity to irreversibly inactivate virus was studied. MPER-specific MAbs potently induced gp120 shedding upon prolonged contact with the virus, rendering neutralization irreversible. The kinetic and thermodynamic requirements of the shedding process were virtually identical to those of neutralization, identifying gp120 shedding as a key process associated with HIV neutralization by MPER bNAbs. Neutralizing and shedding capacity of 7 MPER-, CD4bs- and V3 loop-directed MAbs were assessed against 14 divergent strains. 447-52D induced potent shedding that correlated with its neutralization activity. Ruprecht2011 (neutralization, kinetics)
447-52D: Closely related HIV-1 B clade Envs from a pediatric subject in a late disease differed in their capacity to infect primary macrophages. E153G conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop MAb 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12. Musich2011 (escape)
447-52D: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates. Haldar2011 (neutralization)
447-52D: A way to produce conformationally intact, deglycosylated soluble, cleaved recombinant Env trimers by inhibition of the synthesis of complex N-glycans during Env production, followed by treatment with glycosidases under conditions that preserve Env trimer integrity is described to facilitate crystallography and immunogenicity studies. MAb 447–52D bound more strongly to deglycosylated trimers than untreated ones. Depetris2012 (glycosylation, binding affinity)
447-52D: Masking signatures were developed and analyzed for 4 anti-HIV V3 loop MAbs, 2219, 3074, 2557, 447-52D. The epitopes were classified as "masked" if their signature motifs were present in a virus, but there was no detectible neutralization by the MAb of the same virus in vitro. The signature motif for MAb 2219 used in the study was R9+K10+[l,V]12+[Y,F]21. Of the 4 MAbs, 2219 neutralized the largest number of pseudoviruses containing its epitope. The 2219 neutralization epitope is unmasked in 25/68 (36.8%) of the viruses containing the 2219 epitope. Agarwal2011 (neutralization)
447-52D: One Env clone (4–2.J45) obtained from a recently infected Indian patient (NARI-IVC4) had exceptional neutralization sensitivity compared to other Envs obtained at the same time point from the same patient. The effect of I424M substitution in three clade B Envs (RHPA4259.7, JRFL and YU2) was tested and 2-45-fold increase was found in their sensitivities to anti-V3 MAbs including 447-52D. Ringe2011 (neutralization)
447-52D: Several soluble gp140 Env proteins recognized by PG9 and PG16 were identified, and the effect of Env trimerization, the requirement for specific amino acids at position 160 within the V2 loop, and the importance of proper gp120-gp41 cleavage for MAb binding to soluble gp140s were investigated along with whether and how the kinetics of PG9 and PG16 binding to soluble gp140 correlates with the neutralizing potencies of these MAbs. In some cases the affinities of PG9/PG16 binding were comparable to those of 447-52D. Lower binding affinity of gp140 ligands to PG9/PG16 than 447D was observed. 447-52D binds to an epitope within the V3 loop of gp120 and interacts very efficiently with monomeric gp120. 447-52D also bound to all clade A Env gp140s tested. The anti-SF162 neutralizing activity of 447-52D decreased when the lysine at position 160 was replaced by an asparagine. Davenport2011 (neutralization, binding affinity)
447-52D: The location and extent of conservation of eight protease cleavage sites on HIV-1 gp120 recognized by 3 major human proteases (cathepsins L, S and D) are described along with the effect of cathepsin cleavage on gp120 binding to CD4-IgG and NAbs. 447-52D binding was destroyed with cathepsin L-treated gp120 but preserved with cathepsin D-treated gp120. Yu2010 (binding affinity)
447-52D: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity. Pantophlet2010 (neutralization, variant cross-reactivity, review)
447-52D: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb predominantly neutralizes clade B viruses and occasionally neutralizes some viruses from non-B clades. Gonzalez2010 (neutralization, variant cross-reactivity, escape, review)
447-52D: The expression and characterization of different glycoforms of V3-Fc fusion protein along with its binding to HIV-neutralizing Abs 2G12 and 447-52D was examined. The binding affinity of 447-52D was high for complex type glycoform V3-Fc-CT and high-mannose type glycoforms of V3-Fc (V3-Fc-HM, V3-Fc-M9 and the two mutants:N301A and Fc-N297A) following a quick association/dissociation kinetic process but it was higher for gp120 with extremely slow dissociation process. The affinity to 447-52D was not significantly affected by removal of the N-glycans at the N297, N301 and N332 sites. Yang2010a (glycosylation, binding affinity)
447-D52: This paper shows that a highly neutralization-resistant virus is converted to a neutralization sensitive virus with a rare single mutation D179N in the C-terminal portion of the V2 domain for several antibodies. 447D-52, however, did not neutralize any of the mutants tested. ORourke2010 (neutralization, variant cross-reactivity)
447-52D: A side-by-side comparison was performed on the quality of Ab responses in humans elicited by three vaccine studies focusing on Env-specific Abs. V3 Abs with specificities similar to that of 447-52D were elicited nearly ubiquitously in all of the vaccine sera tested, where the sera were able to outcompete binding to 447-52D. Vaine2010 (antibody interactions)
447-52D: Structure of 447-52D bound to a peptide containing the sequence of the V3 loop was used to derive sensitive and specific signature motifs for its neutralization epitope. 447-52D epitope (¹⁶PxR¹⁸) was found conserved in 11% of circulating HIV-1 strains, and was highly restricted to subtype B strains. 447-52D neutralized 9% of subtype A pseudovirions, 47% of subtype B, 4% of subtype C, 10% of subtype D and 0% of CRF02_AG. Swetnam2010 (antibody binding site, neutralization, variant cross-reactivity, subtype comparisons, structure)
447-52D: Peptide ligands for CD4i epitopes on native dualtropic Envs were selected by phage display. The correct exposure of CD4i epitopes was detected by binding with MAb 447-52D, which bound both in the presence or absence of sCD4. Dervillez2010 (binding affinity)
447-52D: Impact of in vivo Env-CD4 interactions was studied during vaccinations of Rhesus macaques with two Env trimer variants rendered CD4 binding defective (368D/R and 423/425/431 trimers) and wild-type (WT) trimers. Ab binding profiles of the three trimer variants were assessed by binding analyses to different MAbs. V3-directed MAb 447-52D bound similarly to all three trimer variants: WT and 368D/R, and 423/425/431. Douagi2010 (binding affinity)
447-52D: The effect of presence and absence of V1 loop was assessed using two approaches: remove V1 loop from the soluble trimeric gp140 construct (ΔV1SF162gp140) and second, substitute the V1 loop on SF162gp140 construct with four different V1 loops from 89.6, YU2, JRFL, and HxB2 (heterologous HIV-1 viruses). Deletion or substitution of V1 loop increased resistance to neutralization by 447-52D in 3 out of 5 V1-modified gp140 constructs, although it did not affect the binding to 447-52D. D368R modification to SF162gp120 did not affect the binding to 447-52D but there was a decrease in neutralization activity by 447-52D. Ching2010 (neutralization, binding affinity)
447-52d: Clustering analysis was performed to find patterns of neutralization reactivity for the dataset of 103 patients sera against 20 viruses. The clustering by five MAbs (including 447-52d) against the 20 isolates was less statistically robust than that with serum titers, resulting in three clusters for both cases. The membership in an isolate cluster defined by serum titers was compared with its sensitivity to every MAb to understand the relationship of serum and MAb reactivity. Membership in two out of three clusters did not correlate with sensitivity to 447-52d. Doria-Rose2010 (neutralization)
447: 447 neutralizing activity was assessed against pseudoviruses expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infection. IC50 neutralization activity was also statistically assessed based on the area under the neutralization curves (AUC). 447 was able to neutralize 6/57 viruses in U87-based assay and 12/41 viruses in TZM-based assay, including Tier 1 and Tier 2 viruses, viruses of subtypes A, B, C, AG, and viruses from both chronic and acute infections. AUC analysis revealed that 15/57 viruses in the U87-based assay, and 12/41 viruses in the TZM-based assay, were significantly neutralized by this Ab. Thus, the AUC method has the ability to detect low levels of neutralizing activity that otherwise may be missed. Hioe2010 (assay or method development, neutralization, variant cross-reactivity)
447-52D: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 447-52D neutralized all ΔV1V2 variants more potently than wild type virus, indicating better exposure of the 447-52D epitope when V1V2 domain is removed. Bontjer2010 (neutralization)
447-52D: This review discusses recent research done to improve the production, quality, and cross-reactivity of binding Abs, neutralizing Abs, monoclonal Abs with broad neutralizing activity, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI), and catalytic Abs. Studies focusing on several aspects of BNAb roles in vaccine development, and studies done to better understand the broad binding capacity of BNAbs are reviewed. Baum2010 (ADCC, neutralization, review)
447-52D: GnTI virus (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps), and the N301Q mutant virus (glycan at position 301 is removed), were both significantly more sensitive to neutralization by 447-52D compared to the parental virus. This suggests that the antennae of the complex glycans play a significant role in protecting the V3 loop from Ab binding. Binley2010 (glycosylation, neutralization)
447: This human Ab was compared to MAbs 2.2G, 2.3E, 2.5B derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 2909, 830A and sCD4. 447 blocked the capture of virions by MAbs 2.2G, 2.3E, 2.5B and human MAb 2909. 447 capture of virions was partially blocked by 2909 and 830A and not blocked by sCD4. Robinson2010 (binding affinity)
447: Two V3-scaffold immunogen constructs were designed and expressed using 3D structures of cholera toxin B (CTB), V3 in the gp120 context, and V3 bound to 447-52D MAb. The construct (V3-CTB) presenting the complete V3 was recognized by 447-52D and by the large majority of other MAbs (18/24), indicating correctly folded and exposed MAb epitopes. V3-CTB induced V3-binding Abs and Abs displaying cross-clade neutralizing activity in immunized rabbits. Short V3-CTB construct, presenting a V3 fragment in conformation observed in complex with 447-52D, showed high affinity binding to 447-52D. Few other MAbs retained the same binding affinities for this construct as for the V3-CTB, indicating that they utilize a binding mode similar to that of 447-52D. Totrov2010 (vaccine antigen design, binding affinity, structure)
447-52D: A panel of 109 HIV-1 pseudoviruses was assessed for neutralization sensitivities to 447-52D MAb and patient plasma pools from genetically diverse HIV-1 positive samples. Clustering analyses revealed that the 109 viruses could be divided to 4 sub-groups, based on their neutralization sensitivity to the plasma pools: very high (Tier 1A), above-average (Tier 1B), moderate (Tier 2), and low (Tier 3) sensitivity. 3 Tier 1A, 7 Tier 1B, 3 Tier 2 and 1 Tier 3 viruses were found to be sensitive to neutralization by 447-52D. Seaman2010 (neutralization)
447-52D: Neutralizing sensitivity of L669S gp41 mutant virus to 447-52D increased ∼169-fold compared to the wild type virus, indicating that conformational changes in the MPER could alter the exposure of neutralization epitopes in other regions of HIV-1 Env. Shen2010 (neutralization)
447-52D: Neutralization potency of 447-52D was compared to that of HK20 scFv in TZM-based assay using 45 Tier 1 and Tier 2 HIV isolates. 447-52D neutralized 6/45 isolates. Sabin2010 (neutralization, variant cross-reactivity)
447-52D: Crystal structures of 2219, 2557, 1006-15D and 3074 MAbs in complex with V3 peptides revealed that these MAbs bind to conserved elements in four regions of the V3: the arch, the circlet, the band, and the V3 peptide main chain backbone. A mimotope that preserved the key structural elements in the circlet and band regions, but with GPG of the arch replaced by a disulfide bond, interacted with broadly reactive MAbs 2557, 1006 and 2219. It did not react with 447-52D nor 268-D, which are dependent on the Arg in the arch. Thus, mimotopes can be constructed that may focus the immune response on structurally conserved elements. Jiang2010 (antibody binding site, mimotopes, structure)
447-52D: B cell depletion in an HIV-1 infected patient using rituximab led to a decline in NAb titers and rising viral load. Recovery of NAb titers resulted in control of viral load, and the newly emerged virus population was examined. Strong binding competition between patient sera and 447-52D was observed. Huang2010 (antibody interactions)
447-52D: Binding affinity of 447-52D to a minimal peptide was 2-fold weaker than binding of this Ab to gp140 monomers and trimers. The opposite was observed for MAb 4E10. Xu2010 (binding affinity)
447-52D: 447-52D ability to bind different Env trimers and its neutralization breadth are reviewed. This review also summarizes data on the evolution of HIV neutralizing Abs, principles of Env immunogen design to elicit broadly neutralizing Abs, and future critical areas of research for development of an Ab-based HIV vaccine. Hoxie2010 (vaccine antigen design, review)
447-52D: 58 mAbs, including 3 broadly neutralizing mAbs, were isolated from memory B cells of HIV-1 infected donors using an improved EBV immortalization method combined with a broad screening strategy. 447-52D neutralization activity was compared to the three new broadly neutralizing mAbs. 447-52D neutralized 88% of Tier 1 and 4% of Tier 2 viruses, the neutralization of Tier 2 viruses being inferior to that of the new mAbs HGN194 and HJ16. Corti2010 (neutralization)
447-52D: 433 Abs were cloned from HIV envelope-binding memory B cells from 6 patients with broadly neutralizing sera. The Abs had neutralizing activity directed against several epitopes on gp120 and the majority neutralized Tier 1 viruses. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations. 447-52D was used as a control and it neutralized 5/5 Tier 1 and 2/5 Tier 2 viruses. Scheid2009 (neutralization)
447-52D: NAb specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. The integrity and specificity of gp120 beads in adsorption assay were validated by their ability to adsorb binding activity of 447-52D. gp120 point mutation D368R was used to screen the sera for CD4bs- Abs, and it was shown that this mutant could adsorb binding activity of 447-52D. To test for presence of coreceptor binding region MAbs in sera, gp120 I420 mutant was used. This mutant was recognized by 447-52D at equal levels as the wild type. To test sera for presence of V3 neutralizing activity, V3 peptides were used. These peptides inhibited neutralization mediated by 447-52D. In some of the broadly neutralizing sera, the gp120-directed neutralization was mapped to CD4bs. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER. Li2009c (assay or method development)
447-52D: 447-52D sequence-independent mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo. Kwong2009a (antibody binding site, review)
447-52D: The review discusses the implications of HIV-1 diversity on vaccine design and induction of neutralizing Abs, and possible novel approaches for rational vaccine design that can enhance coverage of HIV diversity. Patterns of within-clade and between-clade diversity in core epitopes of known potent neutralizing Abs is displayed. Korber2009 (review)
447-52D: 447-52D bound to both SF162 wild type and SF162 mutant, carrying only the monomeric form of the Env protein, virions and transfected cells. 447-52D exhibited higher binding activity to SF162 wild type compared to 2909, suggesting that 2909 epitope may not be formed on each trimer. Kimura2009 (antibody binding site, binding affinity)
447-D: FcγR-mediated inhibition and neutralization of HIV by 447-D and other MAbs is reviewed. The review also summarizes the role of ADCC and ADCVI Abs on HIV infection inhibition and neutralization. Forthal2009 (review)
447-52D: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for 447-52D were smaller than those for VRC01. Zhou2010 (neutralization, structure)
447-52D: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 447-52D. Memory B cells were selected that bound to RSC3 and full IgG mAbs were expressed. Three newly detected MAb VRC1 did not enhance neutralization by 447-52D. Addition of RSC3 had no effect on 447-52D neutralization of HXB2. Wu2010 (neutralization, binding affinity)
447-52d: Insertion of one or two disulfide bonds at specific residues in a V3 MN peptide sequence was used to constrain the conformations of the peptides to β-hairpin structures recognized by the 447-52d (postulated R5 V3 conformation). Insertion of two disulfide bonds increased the tendency of the peptides to form β-hairpin structures but it required replacement of residues reacting strongly with 447-52d Ab. Thus, peptides constrained by one disulfide bond are suggested to be more attractive candidates for immunogens that could elicit neutralizing Abs. Mor2009 (antibody binding site)
447-52d: The epitope sequence motif of 447-52d was precisely defined based on the 3D structure of the MAb complexed with V3MN peptide. Depending on how snugly V3 loop side chains are bound by the Ab, the complex can be divided into 3 subdomains. The specific epitope motif suggested by the complex structure was shown to be R315. 93% of HIV sequences with R315 in the Los Alamos HIV database fit the ag-binding site of MAb 447-52d. A set of V3 chimeric pseudoviruses, carrying either R315 or Q315, were tested for their sensitivity to neutralization by 447-52d. R315 viruses were neutralized very well while Q315 viruses were neutralized much more weakly. Thus, the sequence motif for the neutralization epitope recognized by 447-52d is R315. The neutralization-relevant epitope sequence motif of 447-52d was calculated to be present in approximately 13% of worldwide HIV isolates, predominating in subtype B isolates. Cardozo2009 (neutralization, optimal epitope)
447-52D: NL4.3 virus was cultured with cyclotriazadisulfonamide (CADA) and CADA-resistant virus was selected. 447-52D MAb showed enhanced binding to the CADA-resistant virus compared to wildtype. In addition, CADA-resistant virus was more susceptible to neutralization by this MAb. The mutations in CADA-resistant virus are suggested to stabilize the conformation of gp120 and reduce glycosylation. Vermeire2009 (neutralization, binding affinity)
447-52D: C2EB5 MAb was isolated from mice immunized with a peptide from C2 region. C2EB5 neutralization and binding affinity to virions of clades A, B, C, D and CRF01_AE was compared to that of 447-52D. Sreepian2009 (neutralization, variant cross-reactivity, binding affinity)
447-52D: Binding of 447-52D to gp120 was not inhibited by YZ23, an Ab derived from mice immunized with eletcrophilic analogs of gp120 (E-gp120), indicating no overlap of these MAb epitopes. Nishiyama2009
447-52D: V3 peptides were constrained in various ways to stabilize the β-hairpin conformation. This study showed that it is possible to constrain V3 peptides to this conformation that is recognized by 447-52D while maintaining high-affinity binding to this Ab. Peptides designed to mimic either the R5A or R5B conformation had higher affinity to 447-52D than peptides designed to mimic X4 conformation. Mester2009 (antibody binding site, kinetics, binding affinity)
447-52D: This Ab neutralized JRFL strain but many folds higher concentrations of the Ab were needed compared to neutralization of SF162 and SS1196 by 447-52D. 447-52D did not neutralize strain 3988.25. Hioe2009 (neutralization)
447-52D: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:3-15*07, IGHD:3-10, D-RF:3, IGHJ:6. There was a preferential usage of the VH5-51 gene segment for V3 Abs. The usage of the VH4 family for the V3 Abs was restricted to only one gene segment, VH4-59, and the VH3 gene family was used at a significantly lower level by these Abs. The V3 Abs preferentially used the JH3 and D2-15 gene segments. Gorny2009 (antibody sequence)
447-52D: An international collaboration (NeutNet) was organized to compare the performance of a wide variety of HIV-1 neutralization assays performed in different laboratories. Four neutralizing agents were evaluated: 4E10, 447-52D, sCD4 and TriMab (equal mixture of 2F5, 2G12 and 4E10). In general, there were clear differences in assay sensitivities that were dependent on both the neutralizing agent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities. Fenyo2009 (assay or method development, neutralization)
447-52D: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimera were sensitive to neutralization by 447-52D, while the wildtype derived viruses HIV-2KR.X4 and HIV-2KR.X7 were completely resistant. A V3 linear peptide from HIV-1 JR-FL was able to absorb all 447-52D neutralizing activity and a peptide from HIV-1 YU2 removed most of the 447-52D neutralizing activity. Fc-V3 fusion proteins from subtypes B and C completely eliminated 447-52D-mediated neutralization. However, 447-52D was unable to neutralize the primary HIV-1 BORI virus while it neutralized the HIV-2-BORI V3 chimera. Competition assays showed that most of the plasmas derived from subtype B and C chronically infected individuals had neutralizing activity that was V3 specific and dependent upon residued in the V3 crown that overlap 447-52D and F425 B4e8 epitopes. Also, 55 early founder viral Env proteins from 47 subjects acutely infected with subtype B virus were tested for susceptibility to 447-52D. 51 viruses were resistant to neutralization by 447-52D, but many showed sensitivity to this Ab once conformational changes were induced with sCD4. This indicates that the V3 region in primary HIV-1 Envs is highly conserved but is shielded from Ab recognition. Davis2009 (HIV-2, neutralization, acute/early infection)
447-52D: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. 447-52D bound detectably to gp120 of CC101.19 but this was greatly reduced compared to the binding of 447-52D to gp120 of the other three viruses. The opposite was true for 447-52D binding to the V3 peptide alone of the four viruses. 447-52D neutralized CC101.19 but did not neutralize the other three viruses. This indicates that the V3 region of CC101.19 has become unusually accessible to V3 Abs. Berro2009 (neutralization, binding affinity)
447-52D: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. 447-52D was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120. Banerjee2009 (binding affinity)
447-52D: Reactivity and structure of 447-52D and 537-10D MAbs was compared. 447-52D was able to bind 22/24 V3 peptides from a panel of clades A, B and C, including peptides with both GPGR and GPGQ motifs, while 537-10D only reacted with peptides containing the GPGR motif. Crystal structures of the Fab fragments of 447-52D and 537-10D in complex with 23-mer peptides derived from clades A and B viruses, respectively, was determined. Although both MAbs had highly similar antigen binding sites, differences in their binding and neutralization activities were found to be due to subtile differences in their structures. The structure analyses explained the ability of 447-52D to bind to both GPGR and GPGQ motifs. Burke2009 (antibody binding site, neutralization, structure)
447-52D: Data is summarized on the X-ray crystal structures resolution and NMR studies of 447-52D. Sirois2007 (review, structure)
447-52D: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb 447-52D in different HIV-1 clades is provided. McKnight2007 (variant cross-reactivity, review)
447-52D: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. 447-52D neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, such as 447-52D, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed. Phogat2007 (review)
447-52D: This review summarizes current knowledge on the various functional properties of antibodies in HIV-1 infection, including 447-52D MAb, in vivo and in vitro activity of neutralizing Abs, the importance and downfalls of non-neutralizing Abs and antibodies that mediate antibody-dependent cellular cytotoxicity and the complement system, and summarizes data on areas that need future investigation on Ab-mediated immune control. Huber2007 (review)
447-52D: 447-52D structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit anti-V3 Abs, are reviewed in detail. Lin2007 (review, structure)
447/52D: This review summarizes 447-52D Ab epitope, properties and neutralization activity. Kramer2007 (review)
447-52D: Current insights into CTLs and NAbs, and their possible protective mechanisms against establishment of persistent HIV/SIV infection are discussed. Pre- and post-infection sterile and non-sterile protection of NAbs against viral challenge, and potential role of NAbs in antibody-mediated antigen presentation in modification of cellular immunity, are reviewed. 447-52D anti-viral activity in suppression of viral rebound in HIV-1 infected humans undergoing structured treatment interruptions is described. Yamamoto2008 (supervised treatment interruptions (STI), review)
447-52D: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All but three of the transmitted or early founder Envs were resistant to neutralization by 447-52D, indicating that the coreceptor binding surfaces on transmitted/founder Envs are conformationally masked. sCD4 could trigger a conformational change in gp120 of these Envs and render the virus susceptible to neutralization by 447-52D. Keele2008 (neutralization, acute/early infection)
447-52D: A significantly higher level of 447-52D bound to gp120 complexed with anti-CD4bs mAbs than to gp120 alone or in complex with other non-CD4bs Abs, indicating that binding of anti-CD4bs Abs to gp120 increases exposure of specific V3 MAb epitopes. Visciano2008 (antibody binding site)
447D: Trimeric envelope glycoproteins with a partial deletion of the V2 loop derived from subtype B SF162 and subtype C TV1 were compared. 447D recognized both B and C trimers with similar efficiency, indicating that the epitope recognized by this Ab is exposed and preserved in the subtype C trimers. Subtype C trimer had many biophysical, biochemical, and immunological characteristics similar to subtype B trimer, except for a difference in the three binding sites for CD4, which showed cooperativity of CD4 binding in subtype C but not in subtype B. Srivastava2008 (binding affinity, subtype comparisons)
447-52D: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 447-52D, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive for neutralization by 447-52D, although 447-52D bound strongly to gp120 from CC1/85 and CC101.19. These results indicate that V3-dependent and -independent changes responsible for CCR5 inhibitor resistance do not necessarily alter the exposure of V3 to some of the V3 Abs. Pugach2008 (co-receptor, neutralization, binding affinity)
447-52D: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. 447-52D belonged to the group 2 MAbs, which are able to bind subtype B but not subtype C gp120, and are able to bind both V3 peptides. 447-52D was able to bind subtype B V3 in the subtype C Env backbone chimera, but not the reverse, indicating that 447-52D binds to a structure created by the subtype B V3 sequence that is not impacted by the gp120 backbone. For subtype B, 447-52D required an R18 residue in order to bind, but the binding was not significantly affected by the H13R change. For subtype C, Q18R mutation did not restore binding to gp120, but the R13H-Q18R double mutation did. Peptide binding was affected only by the R13H mutation, indicating that the poor binding of Q18R gp120 mutant has a structural basis. 447-52D was not able to neutralize JR-FL isolate, and somewhat neutralized SF162. A chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by this Ab. Patel2008 (neutralization, binding affinity, subtype comparisons)
447-52D: Requirements for elicitation of CD4i Abs were examined by immunizing non-primate monkeys, rabbits, and human-CD4 transgenic (huCD4) rabbits with trimeric gp140. The trimers used for the immunizations were inoculated with PBMCs, and CD4-specific binding to live CD3+/CD4+/CD8- cells was verified by recognition of the trimers by 447-52D. Forsell2008
447-52D: To test whether the conformation change of Env induced by CD4 affects the breadth and potency of 447-52D neutralization, 447-52D was tested in the presence or absence of sCD4 in neutralization of a panel of 12 subtype B and 12 subtype C Env-pseudoviruses. Without sCD4, 447-52D neutralized 2 subtype B and 0 subtype C viruses. With sCD4 present, 447-52D neutralized 7 subtype B and 1 subtype C virus, indicating that neutralization resistance of some viruses to 447-52D is due to a lack of exposure of the V3 loop. Neutralization of JRFL, ADA, and YU2 isolates by 447-52D increased with increased dose of sCD4. A virus with GPGG sequence at the tip of the V3 loop did not react with 447-52D, indicating that amino acid sequence variation may account for the neutralization resistance of other viruses. The presence of b12 and F105 did not induce 447-52D mediated neutralization of JRFL virus, indicating that b12 and F105 do not induce a conformation alternation in Env that exposes V3 loop to 447-52D. Wu2008 (neutralization, variant cross-reactivity)
447-52D: The neutralization profile of early R5, intermediate R5X4, and late X4 viruses from a rhesus macaque infected with SHIV-SF162P3N was assessed. The parental R5 virus was resistant to neutralization by 447-52D, while both the R5X4 intermediate and the late X4 viruses were sensitive to neutralization by 447-52D. The enhanced neutralization susceptibility of the dual-tropic and the X4 viruses to 447-52D suggests adoption of an increasingly open conformation of the Env gp120 over time. Tasca2008 (co-receptor, neutralization)
447D: 447D neutralized 6 of the 15 subtype B isolates tested, of which 5 were resistant to neutralization by MAbs 19b, 39F, CO11, F2A3, F530, LA21 and LE311. Angle of interaction between 447D and V3 was shown by superimposing the Fab fragment of the Ab with V3. 447D was shown to interact with V3 from a nearly identical angle as MAb 58.2. Pantophlet2008 (antibody binding site, neutralization, structure)
447-52D: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of 447-52D to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact 447-52D epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Purified gp140DF162ΔV2 was recognized by 447-52D, and the k-off value for 447-52D was reduced compared to gp120SF162 monomer, consistent with the gp140DF162ΔV2 trimeric conformation. Binding of 447-52D to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved. Martin2008 (assay or method development, kinetics, binding affinity)
447-52D: Variable domains of three heavy chain Abs, the VHH, were characterized. The Abs were isolated from llamas, who produce immunoglobulins devoid of light chains, immunized with HIV-1 CRF07_BC, to gp120. It was hypothesized that the small size of the VHH, in combination with their protruding CDR3 loops, and their preference for cleft recognition and binding into active sites, may allow for recognition of conserved motifs on gp120 that are occluded from conventional Abs. 447-52D provided some inhibition of binding of the three neutralizing VHH Abs to gp120, suggesting that 447-52D imposes steric hinderance to binding of the VHH Abs to gp120. Forsman2008 (antibody interactions)
447-52D: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. V3 Ab activity was measured by three assays where 447-52D was used as a control. A V3 peptide derived from the N-terminal part of the V3 loop, including the crown, potently inhibited neutralization of several HIV-1 isolates by 447-52D, indicating that V3 Abs are commonly directed to the N-terminal part of the V3 loop. Binley2008 (neutralization)
447: 32 human HIV-1 positive sera neutralized most viruses from clades A, B, and C. Two of the sera stood out as particularly potent and broadly reactive. Two CD4-binding site defective mutant Env proteins were generated to evaluate whether Abs to the CD4-binding site are involved in the neutralizing activity of the two sera. The integrity of the wildtype and mutant proteins was tested to their reactivity to the 447 Ab. Li2007a (binding affinity)
447-52D: HIV-1 env clones resistant to cyanovirin (CV-N), a carbohydrate binding agent, showed amino acid changes that resulted in deglycosylation of high-mannose type residues in the C2-C4 region of gp120. Compared to their parental virus HIV-1 IIIB, these resistant viruses were over 200 times more sensitive to 447-52D, indicating that deglycosylation in CV-N resistant viruses is likely to make the V3 loop more accessible to Abs. Hu2007 (antibody binding site, neutralization, escape)
447-52D: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. 447-52D captured modestly (but not significantly) fewer mutant pseudovirions than wild type, neutralization was not tested. Dey2008 (binding affinity)
447D: The study explores how the V1 loop of Env influences the neutralization susceptibilities of heterologous viruses to antibodies elicited by the SF162gp140 immunogen. When the V1 loop of the heterologous isolates was replaced by the V1 loop present on the DF162go140 immunogen, these isolates became susceptible to neutralization by anti-V3 MAb 447D, indicating that the V1 loop plays an important role in the resistance of heterologous viruses to neutralization. Ching2008 (neutralization)
447-52D: The study determined a crystal structure of Fab 447-52D in complex with a V3 peptide NNTRKSIHLGPGRAFYATGDIIG at 2.1 A resolution. The structure revealed an extended CDR H3 loop that forms a β-sheet with the peptide, with predominantly main-chain hydrogen bonds contacts. There was high structural homology with reported structures of other Fab 447-52D complexes, indicating that the V3 loop may adopt a small set of conserved structures around the crown of the β-hairpin. Dhillon2008 (structure)
447-52D: 447-52D bound only to V3 peptides from the three isolates (MN, SHIVsf162p3 and clade B consensus) which contain GPGR motif. 447-52D did not recognize one B consensus peptide that did contain GPGR motif. Glycosylation of the position 154 in V1 was more important for the protection of the virus from this Ab than glycosylation of the position 195 in V2. 447-52D neutralized chimeric viruses 89.6/SF162V1, JRFL/SF162V1, YU2/SF162V1 and HxB2/SF162V1 more efficiently than their wildtype counterparts, indicating that the accessibility of the V3 loop is affected by the nature of the V1 loop. Derby2007 (neutralization, binding affinity)
447-52D: The epitope recognition sequence for this Ab was introduced into the corresponding region of SIVmac239 either alone or together with epitopes for Abs 2F5 and 4E10. The infectivity and replicative capacity of SIV239/447-52D and SIV239/447-52D/2F5/4E10 were, however, not detectable and too low, respectively, to be used for further analyses. Yuste2006 (SIV)
447-52D: The neutralizing capacity and binding of this Ab to the V3 region of gp120, as well as resistance to neutralization in different HIV-1 clades are reviewed. Pantophlet2006 (antibody binding site, neutralization, review, subtype comparisons, structure)
447-52D: This Ab was shown to neutralize SF162 and the neutralization sensitivity increased in the SF162 variant with a JR-FL V3 loop, SF162(JR-FL V3). In contrast, a great reduction in sensitivity to neutralization was observed in the SF162(JR-FL V1/V2) variant and was somewhat restored in the SF162(JR-FL V1/V2/V3) variant, indicating that the masking of the V1/V2 loop plays a much greater role in restricting neutralization sensitivity than the variations in V3. This Ab was shown to neutralize viruses with V3 sequences from several different subtypes (B, F, A1, CRF02_AG, H and CRF01_AE) except subtype C. This Ab failed to neutralize SF162(JR-FL V1/V2) with V3 derived from different HIV-1 clades indicating effective V1/V2-mediated masking of several HIV-1 clades. The effect on the neutralization sensitivity of the residue at the crown of the V3 loop (position 18) was shown to be great for this Ab. Krachmarov2006 (neutralization, variant cross-reactivity, subtype comparisons)
447-52D: The G314E escape variant highly resistant to KD-247 was shown to be more sensitive to 447-52D than the wildtype virus. 447-52D was shown to be able to bind well to both mutant and wildtype surface-expressed Envs. Yoshimura2006 (escape, binding affinity)
47-52D: Binding of this Ab to three V3 peptides was compared to binding of Ab 2219 to the same peptides. 447-52D was shown to bind to V3 MN and V3 UG1033 but not to V3 UR29. Stanfield2006 (variant cross-reactivity, binding affinity)
447-52D: This MAb was derived from plasma from a patient with env clade B virus with the GPGR V3 motif. When cross-reactivity was tested, this Ab bound to the V3subtypeB-fusion protein containing GPGR motif but not to the V3subtypeA-fusion protein containing GPGQ motif. This Ab was also shown to be able to neutralize both clade B psSF162 (GPGR) and clade C psMW965 (GPGQ) virus, and four of subtype B and two of non-B primary isolates. Gorny2006 (neutralization, variant cross-reactivity, binding affinity, subtype comparisons)
447-52D: Escape variants with the V3 P313L mutation, or V2 R166K, D167N and P175L mutations, were resistant or partially resistant, respectively, to 447-52D. Binding of 447-52D to surface-expressed Env proteins with the V2 mutations was lowered compared to the binding to viruses with no mutations. Binding to surface-expressed Env proteins with the V3 mutation was comparable to the negative control values. Binding affinity of this Ab for different combinations of V2 and V3 mutants was also tested. Shibata2007 (escape, binding affinity)
447-52D: This Ab was used in the analysis of clade C gp140 (97CN54) antigenicity and was shown to bind with relatively high avidity to the molecule and to dissociate substantially within 420 s. It was also used as a positive control in the neutralization assay. Sheppard2007a (neutralization, variant cross-reactivity, kinetics, binding affinity)
447-52D: Compared to the full-length Con-S gp160, chimeric VLPs containing Con-S ΔCFI gp145 with transmembrane (TM) and cytoplasmic tail (CT) sequences derived from the mouse mammary tumor virus (MMTV), showed higher binding capacity to 447-52D. Chimeric VLPs with only CT derived from MMTV also showed higher binding capacity to 447-52D than the full-length Con-S gp160, however, not as high as the chimeric CT-TM VLPs. Wang2007a (binding affinity)
447-52D: The major infectivity and neutralization differences between a PBMC-derived HIV-1 W61D strain and its T-cell line adapted counterpart were conferred by the interactions of three Env amino acid substitutions, E440G, D457G and H564N. Chimeric Env-pseudotyped virus Ch5, containing all three of the mutations, was more neutralization sensitive to 447-52D than Ch2, which did not contain any of these mutations. Env-pseudotyped viruses containing D457G mutation alone, or in combination with E440G or H564N, were also more sensitive to neutralization by 447-52D than Ch2. Beddows2005a (neutralization)
447-52D: The structure of the 447-52D MAb and its mechanisms of the V3 loop GPGR motif recognition and binding are reviewed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed. Burton2005 (antibody binding site, review, structure)
447-52D: Monomeric gp120 and trimeric gp140CF proteins synthesized from an artificial group M consensus Env gene (CON6) bound well to 447-52D, indicating correct exposure of the 447-52D epitope. Gao2005a (antibody binding site)
447-D: This Ab was used as a control in a peptide adsorption assay. 447-D neutralized the SF162 primary isolate to 95%. When 447-D was pre-incubated with BaL or YU2 V3 loop peptides, nearly all neutralizing activity was inhibited. Grundner2005 (neutralization)
447-52D: The crystal and nuclear magnetic resonance structures of V3-reactive antibody-peptide complexes were examined. 447-52D completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
447-52D: A series of genetically modified Env proteins were generated and expressed in both insect and animal cells to be monitored for their antigenic characteristics. For 447-52D, five of the modified proteins expressed in insect cells, including 3G mutant (mutations in 3 glycosylation sites), dV1V2 mutant (V1V2 deletions), 3G-2G, 3G-dV2, and 3G-dV2-1G (1G being a mutation near the TM domain), showed higher binding than the wildtype. Of these, the 3G-dV2-1G mutant showed highest binding to 447-52D, indicating that glycosylation of the gp41 domain may affect exposure of the V3 loop. Expressed in animal cells, mutants dV2 and 3G-dV1V2 showed increased binding to 447-52D at relatively high Ab concentrations compared to the wildtype Env. Kang2005 (antibody binding site, binding affinity)
447D: Full-length gp160 clones were derived from acute and early human HIV-1 infections and used as env-pseudotyped viruses in neutralization assays for their characterization as neutralization reference agents. 2 out of 19 pseudoviruses were sensitive to neutralization by 447D, as was the SF162.LS strain. Li2005a (assay or method development, neutralization)
447: Pseudoviruses expressing HIV-1 envelope glycoproteins from BL01, BR07 and 89.6 strains were compared in neutralization assays to replication competent clone derived from transfection of 293T cells (IMC-293T) and to the IMC-293T derived from a single passage through PBMC (IMC-PBMC). The neutralization responses of pseudoviruses and corresponding IMC-293T to 447 were similar, while a significant decrease in viral neutralization sensitivity to 447 was observed for the BR07 and 89.6 IMC-PBMC viruses. The decrease was associated with an increase in average virion envelope glycoprotein content on the PBMC-derived virus. Louder2005 (assay or method development, neutralization)
447-52D: The structure of V3 HIV-1 peptides derived from IIIB and MN isolates when bound to 447-52D was determined by NMR. It was observed that the two different V3 peptides assumed same N-terminal strand conformation when bound to this Ab. V3 peptide IIIB bound to Ab 0.5β differed from the same peptide bound to 447-52D by 180 degrees N-terminal chain orientation. It is suggested that the conformation of an Ab-bound V3 peptide is dictated not only by the peptide sequence but also by an induced fit to the specific Ab. Dominant interactions of 447-52D with three conserved N-terminal residues may be responsible for the broadly neutralizing capability of this Ab. Rosen2005 (antibody binding site, co-receptor, variant cross-reactivity, structure)
447-52D: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed. Srivastava2005 (neutralization, variant cross-reactivity, review, subtype comparisons)
447-52D: gp120 alone and gp120 bound to CD4D12 (the first two domains of human CD4) or to M9 (a 27-residue CD4 analog) were used to immunize guinea pigs. Only sera from the gp120-CD4D12 immunized animals showed broadly neutralizing activity. Sera from gp120-CD4D12 and gp120 immunized animals competed equally well with 447-52D, indicating that the V3-loop was accessible in both immunogens. Varadarajan2005 (antibody binding site, vaccine antigen design)
447-52D: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1. McCann2005 (antibody binding site, neutralization, review, structure)
447-52D: MAbs were investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. Visualization of Env-Ab binding was conducted by BN-PAGE band shifts. 447-52D binding to trimer was completely dependent on sCD4, consistent with neutralization. Crooks2005 (antibody binding site, assay or method development, neutralization)
447-52D: This review summarizes data on 447-52D-V3 and 447-52D-V3 peptide X-ray crystallographic structures and NMRs and its neutralization capabilities. The binding mechanism of this Ab to V3 explains its ability to neutralize a wide array of viral isolates. Conformation of the V3 peptide bound to 447-52D is very similar to its conformation when bound to mouse Abs 50.1, 59.1 and 83.1. Stanfield2005 (antibody binding site, neutralization, variant cross-reactivity, review, structure)
447-52D: A T-cell line adapted strain (TCLA) of CRF01_AE primary isolate DA5 (PI) was more neutralization sensitive to 447-52D than the primary isolate. Mutant virus derived from the CRF01_AE PI strain, that lacked N-linked glycosylation at position 197 in the C2 region of gp120, was significantly more sensitive to neutralization by 447-52D then the PI strain. Mutants at positions 138 in V1 and 461/464 in V5 showed lower sensitivity to neutralization by 447-52D. Deglycosylated subtype B mutants at positions 197 and 234 were slightly more neutralizable by 447-52D. Teeraputon2005 (antibody binding site, neutralization, subtype comparisons)
447-52D: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. 447-52D moderately neutralized wildtype virus particles. It effectively bound to nonfunctional monomers but not to gp120-gp41 trimers. Monomer binding did not correlate with neutralization, but it did correlate with virus capture. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization. Moore2006 (antibody binding site, neutralization)
447D: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). 447D recognized SF162gp140 and ΔV2gp140 equally and failed to recognize ΔV2ΔV3gp140 and ΔV3gp140. Derby2006 (antibody binding site)
447-52D: 447-52D was not found to inhibit binding of gp120 to DC-SIGN. This Ab bound to Fc-gp120 construct but not to the chimeras missing the V3 loop. Binley2006 (binding affinity)
447-52D: 29 subtype B V3 peptides were designed and used for immunization of guinea pigs. Peptides that induced Abs that neutralized more than 3 HIV isolates were shown to bind to this Ab better than peptides unable to induce neutralization of any of the HIV-1 primary isolates. Haynes2006 (neutralization, binding affinity)
447-52D: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by 447-52D. Cham2006 (neutralization, variant cross-reactivity, subtype comparisons)
447-52D: Guinea-pigs were immunized with 447-52D epitope inserted at three different surface V3 loop locations in the small Escherichia coli Trx protein in order to generate a competent immunogen. Only one complex was shown to successfully generate anti-V3 Abs capable of out-competing 447-52D binding to gp120 and recognizing the same epitope as this Ab. However, these 447-52D-like Abs were not able to affect neutralization of JRFL and BAL. Chakraborty2006 (neutralization, vaccine antigen design, variant cross-reactivity, binding affinity)
447-52D: The ability of this Ab to inhibit viral growth was increased when macrophages and immature dendritic cells (iDCs) were used as target cells instead of PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs can occur by two distinct mechanisms, neutralization of infectivity involving only the Fab part of the IgG, and, an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles. Holl2006 (dendritic cells)
447-52D: Inhibition of R5 HIV replication by monoclonal and polyclonal IgGs and IgAs in iMDDCs was evaluated. The neutralizing activity of 447-52D was observed to be higher in iMDDCs than in PBLs and PHA-stimulated PBMCs. A 90% reduction of HIV infection was observed without induction of MDDC maturation by this MAb. It was also demonstrated that binding of this MAb to HIV-1 was necessary for inhibition of iMDDC infection. Increased expression of FcγRI on iMDDCs increased inhibition of HIV by 447-52D, suggesting the involvement of this receptor in the HIV-inhibitory activity of this MAb. Holl2006a (neutralization, dendritic cells)
447-52D: The neutralization potency of this Ab against 7 HIV-1 primary isolates was compared to the neutralization potency of the anti-V3 MAb KD-247. Same Ab concentrations were needed for neutralization of the MN, N-NIID, and 92TH022 isolates, while higher concentrations of 447-52D were needed for the neutralization of the rest of the HIV-1 isolates suggesting KD-247 is more potent. Eda2006a
447-52D: In this study the neutralization breadth of F425 B4e8 was assessed using a panel of 40 primary HIV-1 isolates, and 447-52D was found to have a similar profile, and was used as a control to gauge the effects of the amino acid substitutions in the V3 region. As expected, replacing Arg 315 with Ala or Gln and Pro 313 with Ala reduced binding affinity of this 447-52D substantially. Ala substitutions of residues in positions 304-309 and 319-320 also unexpectedly resulted in diminished binding affinity of the Ab. Pantophlet2007 (antibody binding site, subtype comparisons)
447-52D: Z13e1, a high affinity variant of Fab Z13, was identified through targeted mutagenesis and affinity selection against gp41 and an MPER peptide. Z13e1 showed 100-fold improvement in binding affinity for MPER antigens over Z13. 447-52D was used as a control in this study. 447-52D was shown to clearly bind to monomers of gp120-gp41 while trimer binding was negligible, in accordance with its modest neutralization potency against HIV-1 JR-FL. Nelson2007 (vaccine antigen design)
447-52D: G1 and G2 recombinant gp120 proteins, consisting of 2F5 and 4E10, and 4E10 epitopes, respectively, engrafted into the V1/V2 region of gp120, were tested as an immunogen to see if they could elicit MPER antibody responses. Deletion of V1/V2 from gp120, or its replacement with G1 and G2 grafts, did not greatly affect binding of 447-52D to gp120. Shortening of the N and C termini of the V3 loop enhanced the binding of 447-52D. Law2007 (vaccine antigen design)
447-52D: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed. Haynes2006a (neutralization)
447-52D: Viruses from early and late infection of a macaque with SHIV SF162P4 were resistant to contemporaneous serum that had broadly reactive NAbs. SF162 was highly susceptible to neutralization by anti-V3 MAbs 447D and P3E1, as well as anti-V1 MAb P3C8, while envelopes cloned from this animal at 304 days and at 643 days (time of death) post infection had developed resistance to all three of these antibodies. Kraft2007 (neutralization, escape)
447-52D: This Ab was used to help define the antigenic profile of envelopes used in serum depletion experiments to attempt to define the neutralizing specificities of the broadly cross-reactive neutralizing serum. Peptides containing epitopes for 447-52D did not inhibit neutralization by broadly neutralizing sera from two clade B and one clade A infected asymptomatic individuals, indicating that the V3 epitope for this MAb did not account for the broad neutralizing activity observed. 447-52D bound to JR-FL and JR-CSF gp120 monomers but not to core JR-CSF gp120 monomer. Dhillon2007 (antibody binding site, neutralization)
447-52D: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO. Selvarajah2005 (vaccine-induced immune responses, Th2)
447-52D: This study is about the V2 MAb C108g, which is type-specific and neutralizes BaL and HXB2. JR-FL is a neutralization resistant strain; modification of JRFL at V2 positions 167 and 168 (GK->DE) created a C108g epitope, and C108g could potently neutralize the modified JR-FL. The modification in V2 also increased neutralization sensitivity to V3 MAbs 4117c, 2219, 2191, and 447-52D (447-52D was the only one of the 4 V3 MAbs that could neutralize the unmodified JRFL); but only had minor effects on neutralization by CD4BS MAb 5145A, and broadly neutralizing MAbs IgG1b12, 2G12, and 2F5. Pinter2005 (antibody binding site)
447-52D: The HIV-1 Bori-15 variant was adapted from the Bori isolate for replication in microglial cells. Bori-15 had increased replication in microglial cells and a robust syncytium-forming phenotype, ability to use low levels of CD4 for infection, and increased sensitivity to neutralization by sCD4 and 17b. Four amino acid changes in gp120 V1-V2 were responsible for this change. Protein functionality and integrity of soluble, monomeric gp120-molecules derived from parental HIV-1 Bori and microglial-adapted HIV-1 Bori-15 was assessed in ELISA binding assays using CD4BS MAbs F105 and IgG1b12, glycan-specific 2G12, and V3-specific 447-52D, and were unchanged. Association rates of sCD4 and 17b were not changed, but dissociation rates were 3-fold slower for sCD4 and 14-fold slower for 17b. Martin-Garcia2005 (antibody binding site)
447-52D: The epitope for the MAb D19 is conserved and embedded in V3. D19 is unique in that for R5 viruses, it was cryptic and did not bind without exposure to sCD4, and for X4 and R5X4 isolates it was constitutively exposed. It had an overlapping binding region with MAbs 447-52D, B4e8, and 268-D, but different reactivity patterns and fine specificity. While B4e8 and 447-52D could bind to the R5 virus BaL in the absence of sCD4, treatment with sCD4 did increase the binding of both B4e8 and 447-52D, but did not impact their ability to neutralize BaL. Lusso2005 (antibody binding site)
447-52D: Sera from subtype A infected individuals from Cameroon have antibodies that react strongly with subtype A and subtype B V3 loops in fusion proteins, and neutralize SF162 pseudotypes, while sera from 47 subtype B infected individuals reacted only with subtype B. Sera from Cameroon did not neutralize primary A or B isolates, due to indirect masking by the V1/V2 domain rather than due to loss of the target epitope. Neutralization by anti-V3 B clade specific MAbs 447-52D and 4117C was fully blocked by a clade V3 loop fusion protein, but not an A clade fusion protein, while Cameroonian sera neutralization was fully blocked by both A and B clade fusion proteins. Krachmarov2005 (antibody binding site, variant cross-reactivity, subtype comparisons)
447-52D: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. 447-52D has no indication of polyspecific autoreactivity. Haynes2005 (antibody binding site)
447-52d: 2909 is a human anti-Env NAb that was selected by a neutralization assay and binds to the quaternary structure on the intact virion. ELISA-based competition assays and subsequent mutational analysis determined that the CD4BS and V2 and V3 loops contribute to the 2909 epitope: 2909 binding was inhibited by MAbs 447-52d (anti-V3), 830A (anti-V2), and IgG1b12 (anti-CD4BS) and sCD4. 2909 was not inhibited by MAbs 670, 1418, nor 2G12. Gorny2005
447-52D: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 447-52D. Pantophlet2004 (vaccine antigen design)
447-52D: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. Neutralization outside of the B clade was very rare, and seemed to depend on the presence of a GPGR V3 tip, which is rare outside of the B clade. Binley2004 (variant cross-reactivity, subtype comparisons)
447-52D: Analysis of the conformation of 447-52D in complex with the V3MN18 peptide (gp12 aa 310-329, KRKRIHIGPGRAFYTTKN) was undertaken using solid state NMR. The bound peptide had a well-defined constrained structure that was in good agreement with solution NMR and crystallographic studies. Sharpe2004 (structure)
447-52D: A primary isolate, CC1/85, was passaged 19 times in PBMC and gradually acquired increased sensitivity to FAb b12 and sCD4 that was attributed to changes in the V1V2 loop region, in particular the loss of a potential glycosylation site. The affinity for sCD4 was unchanged in the monomer, suggesting that the structural impact of the change was manifested at the level of the trimer. The passaged virus, CCcon19, retained an R5 phenotype and its neutralization susceptibility to other Abs was essentially the same as CC1/85. 447-52D did not neutralize the primary or passaged variant. Pugach2004 (variant cross-reactivity, viral fitness and reversion)
447-52D: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. 5/6 anti-V3 MAbs, including 447-52D, had similar binding affinity to soluble SF162 and JR-FL rgp120s, although the V3 loop differs at three positions (HigpgrafyTtgE for JR-FL and TigpgrafyAtgD for SF162). Pinter2004 (variant cross-reactivity)
447-52D: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the any of three glycans within or adjacent to the V3 loop (GM299 V3), C2 (GM292 C2), C3 (GM329 C3) increased neutralization susceptibility to 447-52D, but C4 (GM438 C4) or V5 (GM454 V5) removal did not make SF162 more sensitive. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes. McCaffrey2004 (antibody binding site, vaccine antigen design)
447-52D: The role of serine proteases on HIV infection was explored. Trypsin decreased the binding of most Env MAb tested and diminished cell fusion of H9 cells infected with HIV-1 LAI virus (H9/IIIB) to MAGI cells. In contrast, thrombin increased the binding of MAbs to gp120 epitopes near the CD4 and CCR5 binding sites, and increased cell fusion. Binding of the V3 MAbs 694-98D and 447-52D, that both bind near the tip of the loop, was decreased by both thrombin and trypsin. Ling2004 (antibody binding site)
447-52D: V3 MAb neutralization is influenced by retaining the epitope, exposure on the intact virion, mobility during CD4-induced conformational change, and affinity. Anti-V3 MAbs selected using V3 peptides neutralize less effectively than V3 MAbs selected using fusion proteins or gp120, suggesting antigenic conformation is important. This MAb was selected using V3 peptides, but was an exception in that it is cross-neutralizing. 447-52D neutralized 12/13 clade B viruses. Gorny2004 (antibody binding site)
447-52D: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates. The set that can cross-neutralize primary isolates (2182, 2191, 2219, 2412, 2442, 2456) bind V3 but are conformationally sensitive, suggesting some structural conservation despite sequence variation. These MAbs have distinct epitopes relative to 447-52D, a MAb directed at the tip of the V3 loop that also can neutralize many primary isolates. Although 447-52D was selected using a peptide, it has conformational characteristics. Inter-clade cross-neutralization by anti-V3 conformation-dependent MAbs is reduced. Gorny2003 (antibody binding site, review)
447-52D: This paper attempts to engineer a gp120 molecule that would focus the immune response onto the IgG1b12 epitope. Adding a glycosylation sequon (P313N) to the V3 loop knocked out binding to anti-V3 MAbs loop 2, 19b and 447-52-D. Pantophlet2003b (vaccine antigen design)
447-52D: scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the V3 MAbs used. Zwick2003a (antibody interactions)
447-52D: The Fv fragment (composed of just the light and heavy variable regions, and the smallest intact binding unit of an Ab) of 447-52 D was expressed and purified. Preliminary NMR with the peptide epitope indicates that an NMR structure determination is feasible. Kessler2003 (antibody sequence, structure)
447-52D: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. 447-52D was able to neutralize the SOS protein better than the wildtype, but did not neutralize SOS well when added post-attachment, as the V3 loop is involved in co-receptor engagement. Binley2003 (vaccine antigen design)
447-52D: Virion capture assays are not a good predictor of neutralization, and the presentation of epitopes using this assay seems to be different from that of functional Envelope spikes on primary isolates -- F105 and b6 could efficiently block the b12-mediated capture of infectious virions in a virus capture, but did not inhibit b12 neutralization -- Ab 447-52D was able to potently neutralize 89.6 and to neutralize JR-CSF at a high concentration but poorly neutralized ADA -- b12 was potent at neutralizing the three primary virions JR-CSF, ADA, and 89.6, but anti-V3 Abs 447-52D and 19b, which did not neutralize JR-CSF and ADA, captured amounts of p24 equal to or higher than the amounts captured by the neutralizing Ab b12. Poignard2003 (antibody binding site, assay or method development, variant cross-reactivity)
447-52D: Review of NAbs. Ferrantelli2002
447-52D: Transgenic mice carrying human genes allowing production of fully human MAbs were used to rapidly create a panel of anti-HIV gp120 MAb producing hybridomas by immunization with HIV SF162 gp120 -- the previously described human MAbs 5145A(CD4BS) , 4117C (plus others, V3) and 697D (and SC258, V2) were used as controls. He2002
447-52D: Conformation-dependent anti-V3 loop Abs may be more cross-reactive, so six new V3 MAbs were generated -- the six new MAbs all bind to the tip of the V3 loop and cross-compete with the MAb 447-52D and are conformationally sensitive -- MAbs showed cross-clade binding to native, intact virions of clades A(N=2), B(N=4), and F(N=2), limited binding to C(N=3) and D(N=3), and did not bind to CRF01(subtype E, N=2) -- the strength binding was highly correlated with percent neutralization using the ghost cell or PHA blast assay -- five well-characterized MAbs were used as controls: anti-V3 447-52D (anti-V3 MAb for competition and neutralization studies), 654 (anti-CD4BS used as a conformation-sensitive MAb control), 1331A (anti-C5 used as a linear binding site MAb control), MAb 246 (anti-gp41 MAb that bound to primary isolates of all clades) -- 447-52D bound to primary isolates from all clades except CRF01 (E), was conformationally sensitive and showed the some of the most potent neutralizing activity. Gorny2002 (variant cross-reactivity)
447-52D: The feasibility of determining the NMR structure of the V3(MN) peptide bound to the 447-52D Fab fragment was tested and a general strategy for obtaining NMR structures of V3 peptide-Fab fragments developed -- preliminary NMR spectra for 447-52D complexed to a 23 amino acid V3 peptide was obtained. Sharon2002 (structure)
447-52D: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent---antigen capture ELISA was used to compare the antigenicity of gp120 and o-gp140 using a panel of well characterized MAbs---447-D recognized the gp120 monomer much more readily than o-gp140, suggesting the V3 loop is less exposed on o-gp140 and on intact virions. Srivastava2002 (antibody binding site, vaccine antigen design)
447-52D: A panel of 12 MAbs was used to identify those that could neutralize the dual-tropic primary isolate HIV-1 89.6 -- six gave significant neutralization at 2 to 10 ug/ml: 2F5, 50-69, IgG1b12, 447-52D, 2G12, and 670-D six did not have neutralizing activity: 654-D, 4.8D, 450-D, 246-D, 98-6, and 1281 -- no synergy, only additive effects were seen for pairwise combinations of MAbs, and antagonism was noted between gp41 MAbs 50-69 and 98-6, as well as 98-6 and 2F5. Verrier2001 (antibody interactions, variant cross-reactivity)
447-52D: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding -- the dissociation constant, Kd of 447-52D for the cell associated primary and TCLA Envs was equal, 3nM. York2001 (antibody binding site, variant cross-reactivity, binding affinity)
447-52D: Six mutations in MN change the virus from a high-infectivity neutralization resistant phenotype to low-infectivity neutralization sensitive -- V3, CD4BS, and CD4i MAbs are 20-100 fold more efficient at neutralizing the sensitive form -- the mutation L544P reduced binding of all MAbs against gp120 by causing conformational changes. Park2000 (antibody binding site)
447-52D: A panel of 47 human MAbs was tested against 26 HIV-1 group M primary isolates from clades A through H -- 19 V3 MAbs were tested, and of 494 combinations, 44% displayed some viral binding -- V3 MAbs tended to have the most cross-reactive binding to clade A, B, C, and D isolates, less to E, F, G, and H -- 447-52D showed the highest cross-reactivity, bound to 24/26 viruses tested, but achieved 90% neutralization only against MN, 50% against CA5, and no neutralization was observed for 3 other isolates tested. Nyambi2000 (subtype comparisons)
447-52D: Called 447D -- SF162 is a neutralization-resistant HIV-1 isolate -- N-linked glycosylation modifications in the V2 loop of the SF162 gp120 revealed that these sites prevent neutralization by CD4BS MAbs (IgG1b12 and IgGCD4), and protect against neutralization by V3 MAbs (447D and 391-95D) -- V2-region glycosylation site mutations did not alter neutralization resistance to V2 MAbs (G3.4 and G3.136) or CD4i MAbs (17b and 48d) -- V2 glycosylation site modification allows infection of macrophages, probably due to glycosylated forms requiring fewer CCR5 molecules for viral entry. Ly2000 (antibody binding site)
447-52D: Ab responses, because of their capacity to alter antigen uptake and processing, can influence helper T cell responses -- CD4BS MAbs or serum Ig from HIV+ individuals inhibited proliferative responses of gp120 specific T cells -- V3 MAbs 447-52-D and 268-10-D did not affect proliferation. Hioe2000
447-52D: To determine the antigenicity of virus killed by thermal and chemical inactivation, retention of conformation-dependent neutralization epitopes was examined, and exposure of CD4BS epitopes was found to be enhanced (MAbs IgG1b12, 205-46-9, and 205-43-1) -- binding to 2G12 and 447-52D epitopes was essentially unaltered -- the 17b CD4i epitope was also exposed. Grovit-Ferbas2000 (vaccine antigen design)
447-52D: Binding of panel of 21 MAbs to soluble oligomeric gp140 versus gp41 or gp120 monomers was compared -- no MAb was oligomer specific, though anti-V3 and CD4BS MAbs reacted better with the oligomer and V2 and C5 tended to favor the monomer -- V3 MAbs 447-52D, 838-D, and 1334 bound with a 7-10 fold preference for the oligomer. Gorny2000b (antibody binding site)
447-52D: rgp120 derived from a R5X4 subtype B virus, HIV-1 W61D, was used to vaccinate healthy volunteers and the resulting sera were compared with sera from HIV-1 positive subjects and neutralizing MAbs -- TCLA strains showed enhanced 447-52D neutralization sensitivity relative to PBMC-adapted lines (32X increase between HIV-1(M2424/PBMC(p0)) and HIV-1(M2424/H9(p9)) and a >128X increase between HIV-1(W61D/PBMC) and HIV-1(W61D/SupT1) isolates) Beddows1999 (variant cross-reactivity)
447-52D: The presence of leukocyte function-associated molecule 1 (LFA-1) promotes virus infectivity and hinders neutralization, and anti-LFA-1 MAbs can enhance the neutralizing effect of anti-HIV V3 MAb 447-52D and anti-HIV CD4BS MAb IgG1b12 -- non-neutralizing anti-HIV CD4BS MAb 654-D did not become neutralizing in the presence of anti-LFA-1 MAbs. Hioe1999
447-52D: MAb peptide-reactivity pattern clustered with the immunological related MAbs: 1334, 419, 504, 447, 453 and 537 -- the core amino acids GP tended to be critical for reactivity in this group -- 447 reacted with peptides containing GPGR, but also with many lacking this sequence (GPGQ, for example), and it failed to react with 2/14 peptides containing GPGR, illustrating the importance of context. Zolla-Pazner1999a (antibody binding site, variant cross-reactivity)
447-52D: Review of clade specificity and anti-V3 HIV-1-Abs. Zolla-Pazner1999b (review, subtype comparisons)
447-52D: Using a whole virion-ELISA method, 18 human MAbs were tested for their ability to bind to a panel of 9 viruses from clades A, B, D, F, G, and H -- 447-52D was the most potent and cross-reactive of 18 human MAbs tested and was the only MAb which bound to virions from isolates CA20 (subtype F), CA13 (subtype H), and VI526 (subtype G) Nyambi1998 (subtype comparisons)
447-52D: Kinetic parameters were measured, and the association rates were similar, but dissociation rate constants were quite variable for V3 MAbs, 1324E was comparable to 447-52D. Gorny1998 (kinetics)
447-52D: Ab from gp120 vaccinated individuals prior to infection, who subsequently became HIV infected, could not achieve 90% neutralization of the primary virus by which the individuals were ultimately infected -- these viruses were not particularly refractive to neutralization, as determined by their susceptibility to neutralization by MAbs 2G12, IgG1b12, 2F5 and 447-52D. Connor1998
447-52D: The MAb and Fab binding to the oligomeric form of gp120 and neutralization were highly correlated -- authors suggest that neutralization is determined by the fraction of Ab sites occupied on a virion irrespective of the epitope. Parren1998 (antibody binding site)
447-52D: Called 447-52-D -- The tip of the MN V3 loop was inserted into cold causing human rhinovirus 14 (HRV14) -- chimeras were immunoselected, and chimeric viruses were neutralized by anti-V3 loop antibodies, and 447-52D was among the Abs used -- chimeric viruses elicited potent NAbs in guinea pigs against ALA-1 and MN. Smith1998 (vaccine antigen design)
447-52D: Inhibits binding of Hx10 to both CD4 positive and negative HeLa cells. Mondor1998 (variant cross-reactivity)
447-52D: Called 447-D -- 447-D resistance took longer to acquire in virus with the M184V substituted RT, and had the form (AAC N to TAC Y) at position 5 of the V3 loop, rather than the GPGR to GPGR resistance found with wildtype RT. Inouye1998
447-52D: Used as a control for comparison to five V3 RF selected antibodies -- 447-52D was reactive with A, B, and C clade peptides, but not E. Gorny1997 (subtype comparisons)
447-52D: Abs that recognize discontinuous epitopes can identify mimotopes from a phage peptide display library -- 447-52D has an epitope involving the tip of the V3 loop, that was previously studied with this method Keller1993 -- in Keller et al., with no competition, LxGPxR was the most common six-mer, 38% of the peptides -- after competition with a gp120 IIIB ligand (QRGPGR)i, RGPxR was the most common and one peptide had the sequence QRGPGR, showing type specific mimotopes can be enriched by strain specific ligand competition protocols Boots1997. Boots1997,Keller1993 (antibody binding site, mimotopes)
447-52D: Called 447 -- gp120 can inhibit MIP-1alpha from binding to CCR5, but this inhibitory effect is blocked by pre-incubation of gp120 with three anti-V3 MAbs: 447, 257, 1027 -- MAb 670 which binds in the C5 region had no effect. Hill1997 (co-receptor)
447-52D: Neutralizes TCLA strains but not primary isolates. Parren1997 (variant cross-reactivity)
447-52D: Viral binding inhibition by 447-D was correlated with neutralization (all other neutralizing MAbs tested showed some correlation except 2F5) Ugolini1997 (antibody binding site)
447-52D: Four primary isolates showed distinct patterns of sensitivity to neutralization by polyclonal sera or plasma and MAbs -- BZ167 was the only isolate inhibited by all polyclonal sera and plasma tested, and was also neutralized by 8/17 MAbs, in particular anti-V3 loop (419-D, 447-52D, 782-D, and 838-D), anti-CD4bd (559/64-D, 654-D and 830-D and a cluster II of gp41 directed MAb (98-6) -- isolates 92HT593 and 91US056 were neutralized by V3 loop (419-D, and 447-52D)and cluster II gp41 (98-6) MAbs at higher concentrations -- US4 was neutralized by some of the polyclonal sera/plasma tested and not at all by MAbs individually or by a cocktail of ten MAbs consisting of 419-D, 447-52D, 782-D, 838-D, 559/64-D, 654-D, 450-D, 670-D, 1281-D and 98-6. Hioe1997b (variant cross-reactivity)
447-52D: Tested using a resting cell neutralization assay. Hioe1997 (assay or method development)
447-52D: Study shows neutralization is not predicted by MAb binding to JRFL monomeric gp120, but is associated with oligomeric Env binding -- 447-52D bound monomer, oligomer, and neutralized JRFL. Fouts1997 (antibody binding site)
447-52D: In a multilaboratory blinded study, failed to consistently neutralize any of nine B clade primary isolates -- many of these isolates had the GPGR motif at the apex of the V3 loop. DSouza1997 (assay or method development, variant cross-reactivity)
447-52D: Review: called 447-52-D -- only four epitopes have been described which can stimulate a useful neutralizing response to a broad spectrum of primary isolates, represented by the binding sites of MAbs: 447-52-D, 2G12, Fab b12, and 2F5. Sattentau1996 (variant cross-reactivity, review)
447-52D: Neutralizes JR-FL -- strongly inhibits gp120 interaction with CCR-5 in a MIP-1beta-CCR-5 competition study. Trkola1996b (co-receptor, variant cross-reactivity)
447-52D: Called 447-52-D -- The sulfated polysaccharide curdlan sulfate (CRDS) binds to the Envelope of T-tropic viruses and neutralizes virus -- CRDS inhibits 447-52D binding. Jagodzinski1996 (antibody binding site)
447-52D: Neutralizing, no viral enhancing activity. Epitope provided as GPGR, but no details are given. Forthal1995 (complement, enhancing activity)
447-52D: Review: the V3 loop motif GPGR is not common outside subtype B isolates, MAb 19b is more cross-reactive than 447-52D. Moore1995c (variant cross-reactivity)
447-52D: Binding affected by identity of amino acids flanking GPGR core -- poor breadth of primary virus neutralization. Moore1995b (variant cross-reactivity)
447-52D: Neutralization of primary and prototype laboratory HIV-1 isolates using a resting cell assay enhances sensitivity. Zolla-Pazner1995a (assay or method development, variant cross-reactivity)
447-52D: Serotyping study using flow-cytometry -- bound only to GPGR V3 loop tips. Zolla-Pazner1995 (antibody binding site)
447-52D: Ab-mediated activation of complement on HIV+ cells is higher than Ab independent activation---what has been termed ''Ab independent'' in fact results in part from IgM in normal human serum that is HIV-cross-reactive. Saarloos1995 (complement)
447-52D: Called 447 -- The tip of the V3 loop was presented in a mucin backbone -- higher valency correlates with stronger affinity constant. Fontenot1995 (vaccine antigen design)
447-52D: Called 447d -- Formalin inactivation of virus at 0.1% formalin for 10 hours at 4 degrees was optimal for inactivation of virus while maintaining epitope integrity. Sattentau1995 (vaccine antigen design)
447-52D: Competition studies with human sera from seroconverting individuals showed that anti-CD4 BS antibodies can arise very early in infection, comparable or prior to anti-V3 antibodies. Moore1994d (acute/early infection)
447-52D: Mild oxidation of carbohydrate moieties does not alter binding. Gorny1994 (antibody binding site)
447-52D: GPGQ in MAL resulted in enhanced dissociation -- GPGQ in CM234 or K14T did not bind -- binding affected by identity of amino acids flanking GPGR core. VanCott1994 (antibody binding site)
447-52D: Neutralization synergy in combination with CD4 binding domain MAbs. Laal1994 (antibody interactions)
447-52D: Requires GPxR at the tip of the V3 loop, common in B clade -- neutralized primary isolates. Conley1994 (antibody binding site, variant cross-reactivity)
447-52D: Complement mediated virolysis of IIIB, but not in the presence of sCD4. Spear1993 (complement)
447-52D: Additive neutralization of MN and SF2 when combined with CD4 binding site MAb F105 -- supra-additive neutralization of RF. Cavacini1993 (antibody interactions)
447-52D: Peptide phage library showed that any of the residues ADGLMNQRS in the X position tolerated in peptides that react well with the antibody. Keller1993 (antibody binding site, variant cross-reactivity)
447-52D: Neutralizes MN and IIIB: GPGR, and binds SF2: GPGR. Gorny1993 (variant cross-reactivity)
447-52D: Reacts with MN, NY5, CDC4, SF2, RF, WM52, and HXB2. Karwowska1992a (variant cross-reactivity)
447-52D: Describes production of mAb 447-D by EBV transformation of PBMC from an HIV-infected individual, followed by fusion with a heteromyeloma. 60-fold increase in neutralization potency when combined 1:1 with human MAb 588-D. Buchbinder1992 (antibody generation, antibody interactions)
447-52D: Requires GPXR at the tip of the V3 loop -- neutralizes a broad array of B clade lab isolates. Gorny1992 (antibody binding site, antibody generation, variant cross-reactivity)

References

Showing 222 of 222 references.

Isolation Paper
Buchbinder1992 A. Buchbinder, S. Karwowska, M. K. Gorny, S. T. Burda, and S. Zolla-Pazner. Synergy between Human Monoclonal Antibodies to HIV Extends Their Effective Biologic Activity against Homologous and Divergent Strains. AIDS Res. Hum. Retroviruses, 8:425-427, 1992. The anti-gp120 V3 MAb 447-D and the anti- gp120 CD4 BS MAb 588-D showed synergistic neutralization. PubMed ID: 1466965. Show all entries for this paper.

Agarwal2011 Alpna Agarwal, Catarina E. Hioe, James Swetnam, Susan Zolla-Pazner, and Timothy Cardozo. Quantitative Assessment of Masking of Neutralization Epitopes in HIV-1. Vaccine, 29(39):6736-41, 9 Sep 2011. PubMed ID: 21216319. Show all entries for this paper.

Banerjee2009 Kaustuv Banerjee, Sofija Andjelic, Per Johan Klasse, Yun Kang, Rogier W. Sanders, Elizabeth Michael, Robert J. Durso, Thomas J. Ketas, William C. Olson, and John P. Moore. Enzymatic Removal of Mannose Moieties Can Increase the Immune Response to HIV-1 gp120 In Vivo. Virology, 389(1-2):108-121, 20 Jun 2009. PubMed ID: 19410272. Show all entries for this paper.

Baum2010 Linda L. Baum. Role of Humoral Immunity in Host Defense Against HIV. Curr HIV/AIDS Rep, 7(1):11-18, Feb 2010. PubMed ID: 20425053. Show all entries for this paper.

Beauparlant2017 David Beauparlant, Peter Rusert, Carsten Magnus, Claus Kadelka, Jacqueline Weber, Therese Uhr, Osvaldo Zagordi, Corinna Oberle, Maria J. Duenas-Decamp, Paul R. Clapham, Karin J. Metzner, Huldrych F. Gunthard, and Alexandra Trkola. Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality. PLoS Pathog, 13(3):e1006255 doi, Mar 2017. PubMed ID: 28264054 Show all entries for this paper.

Beddows1999 S. Beddows, S. Lister, R. Cheingsong, C. Bruck, and J. Weber. Comparison of the Antibody Repertoire Generated in Healthy Volunteers following Immunization with a Monomeric Recombinant gp120 Construct Derived from a CCR5/CXCR4-Using Human Immunodeficiency Virus Type 1 Isolate with Sera from Naturally Infected Individuals. J. Virol., 73:1740-1745, 1999. PubMed ID: 9882391. Show all entries for this paper.

Beddows2005a Simon Beddows, Natalie N. Zheng, Carolina Herrera, Elizabeth Michael, Kelly Barnes, John P. Moore, Rod S. Daniels, and Jonathan N. Weber. Neutralization Sensitivity of HIV-1 Env-Pseudotyped Virus Clones is Determined by Co-Operativity between Mutations Which Modulate the CD4-Binding Site and Those That Affect gp120-gp41 Stability. Virology, 337(1):136-148, 20 Jun 2005. PubMed ID: 15914227. Show all entries for this paper.

Binley2003 James M. Binley, Charmagne S. Cayanan, Cheryl Wiley, Norbert Schülke, William C. Olson, and Dennis R. Burton. Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions. J. Virol., 77(10):5678-5684, May 2003. PubMed ID: 12719560. Show all entries for this paper.

Binley2006 James M. Binley, Stacie Ngo-Abdalla, Penny Moore, Michael Bobardt, Udayan Chatterji, Philippe Gallay, Dennis R. Burton, Ian A. Wilson, John H. Elder, and Aymeric de Parseval. Inhibition of HIV Env Binding to Cellular Receptors by Monoclonal Antibody 2G12 as Probed by Fc-Tagged gp120. Retrovirology, 3:39, 2006. PubMed ID: 16817962. Show all entries for this paper.

Binley2008 James M. Binley, Elizabeth A. Lybarger, Emma T. Crooks, Michael S. Seaman, Elin Gray, Katie L. Davis, Julie M. Decker, Diane Wycuff, Linda Harris, Natalie Hawkins, Blake Wood, Cory Nathe, Douglas Richman, Georgia D. Tomaras, Frederic Bibollet-Ruche, James E. Robinson, Lynn Morris, George M. Shaw, David C. Montefiori, and John R. Mascola. Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C. J. Virol., 82(23):11651-11668, Dec 2008. PubMed ID: 18815292. Show all entries for this paper.

Bricault2018 Christine A. Bricault, James M. Kovacs, Alexander Badamchi-Zadeh, Krisha McKee, Jennifer L. Shields, Bronwyn M. Gunn, George H. Neubauer, Fadi Ghantous, Julia Jennings, Lindsey Gillis, James Perry, Joseph P. Nkolola, Galit Alter, Bing Chen, Kathryn E. Stephenson, Nicole Doria-Rose, John R. Mascola, Michael S. Seaman, and Dan H. Barouch. Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J. Virol., 92(13), 1 Jul 2018. PubMed ID: 29643249. Show all entries for this paper.

Burke2009 Valicia Burke, Constance Williams, Madhav Sukumaran, Seung-Sup Kim, Huiguang Li, Xiao-Hong Wang, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Structural Basis of the Cross-Reactivity of Genetically Related Human Anti-HIV-1 mAbs: Implications for Design of V3-Based Immunogens. Structure, 17(11):1538-1546, 11 Nov 2009. PubMed ID: 19913488. Show all entries for this paper.

Burton2005 Dennis R. Burton, Robyn L. Stanfield, and Ian A. Wilson. Antibody vs. HIV in a Clash of Evolutionary Titans. Proc. Natl. Acad. Sci. U.S.A., 102(42):14943-14948, 18 Oct 2005. PubMed ID: 16219699. Show all entries for this paper.

Cai2017 Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421. Show all entries for this paper.

Carbonetti2014 Sara Carbonetti, Brian G. Oliver, Jolene Glenn, Leonidas Stamatatos, and D. Noah Sather. Soluble HIV-1 Envelope Immunogens Derived from an Elite Neutralizer Elicit Cross-Reactive V1V2 Antibodies and Low Potency Neutralizing Antibodies. PLoS One, 9(1):e86905, 2014. PubMed ID: 24466285. Show all entries for this paper.

Cardozo2009 Timothy Cardozo, James Swetnam, Abraham Pinter, Chavdar Krachmarov, Arthur Nadas, David Almond, and Susan Zolla-Pazner. Worldwide Distribution of HIV Type 1 Epitopes Recognized by Human Anti-V3 Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 25(4):441-450, Apr 2009. PubMed ID: 19320565. Show all entries for this paper.

Cavacini1993 L. A. Cavacini, C. L. Emes, J. Power, A. Buchbinder, S. Zolla-Pazner, and M. R. Posner. Human Monoclonal Antibodies to the V3 Loop of HIV-1 gp120 Mediate Variable and Distinct Effects on Binding and Viral Neutralization by a Human Monoclonal Antibody to the CD4 Binding Site. J. Acquir. Immune Defic. Syndr., 6:353-358, 1993. PubMed ID: 8455141. Show all entries for this paper.

Chakraborty2006 Kausik Chakraborty, Venuka Durani, Edward Roshan Miranda, Michael Citron, Xiaoping Liang, William Schleif, Joseph G. Joyce, and Raghavan Varadarajan. Design of Immunogens That Present the Crown of the HIV-1 V3 Loop in a Conformation Competent to Generate 447-52D-Like Antibodies. Biochem. J., 399(3):483-491, 1 Nov 2006. PubMed ID: 16827663. Show all entries for this paper.

Ching2008 Lance K. Ching, Giorgos Vlachogiannis, Katherine A. Bosch, and Leonidas Stamatatos. The First Hypervariable Region of the gp120 Env Glycoprotein Defines the Neutralizing Susceptibility of Heterologous Human Immunodeficiency Virus Type 1 Isolates to Neutralizing Antibodies Elicited by the SF162gp140 Immunogen. J. Virol., 82(2):949-956, Jan 2008. PubMed ID: 18003732. Show all entries for this paper.

Ching2010 Lance Ching and Leonidas Stamatatos. Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop. J. Virol., 84(19):9932-9946, Oct 2010. PubMed ID: 20660181. Show all entries for this paper.

Conley1994 A. J. Conley, M. K. Gorny, J. A. Kessler, II, L. J. Boots, M. Ossorio-Castro, S. Koenig, D. W. Lineberger, E. A. Emini, C. Williams, and S. Zolla-Pazner. Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates by the Broadly Reactive Anti-V3 Monoclonal Antibody 447-52D. J. Virol., 68:6994-7000, 1994. PubMed ID: 7933081. Show all entries for this paper.

Connor1998 R. I. Connor, B. T. Korber, B. S. Graham, B. H. Hahn, D. D. Ho, B. D. Walker, A. U. Neumann, S. H. Vermund, J. Mestecky, S. Jackson, E. Fenamore, Y. Cao, F. Gao, S. Kalams, K. J. Kunstman, D. McDonald, N. McWilliams, A. Trkola, J. P. Moore, and S. M. Wolinsky. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J. Virol., 72:1552-76, 1998. No gp120-vaccine induced antibodies in a human trial of gp120 MN and SF2 could neutralize the primary viruses that infected the vaccinees. The primary isolates from the infected vaccinees were shown not to be particularly refractive to neutralization by their susceptibility to a panel of neutralizing MAbs. PubMed ID: 9445059. Show all entries for this paper.

Corti2010 Davide Corti, Johannes P. M. Langedijk, Andreas Hinz, Michael S. Seaman, Fabrizia Vanzetta, Blanca M. Fernandez-Rodriguez, Chiara Silacci, Debora Pinna, David Jarrossay, Sunita Balla-Jhagjhoorsingh, Betty Willems, Maria J. Zekveld, Hanna Dreja, Eithne O'Sullivan, Corinna Pade, Chloe Orkin, Simon A. Jeffs, David C. Montefiori, David Davis, Winfried Weissenhorn, Áine McKnight, Jonathan L. Heeney, Federica Sallusto, Quentin J. Sattentau, Robin A. Weiss, and Antonio Lanzavecchia. Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals. PLoS One, 5(1):e8805, 2010. PubMed ID: 20098712. Show all entries for this paper.

Crooks2005 Emma T. Crooks, Penny L. Moore, Douglas Richman, James Robinson, Jeffrey A. Crooks, Michael Franti, Norbert Schülke, and James M. Binley. Characterizing Anti-HIV Monoclonal Antibodies and Immune Sera by Defining the Mechanism of Neutralization. Hum Antibodies, 14(3-4):101-113, 2005. PubMed ID: 16720980. Show all entries for this paper.

Davenport2011 Thaddeus M. Davenport, Della Friend, Katharine Ellingson, Hengyu Xu, Zachary Caldwell, George Sellhorn, Zane Kraft, Roland K. Strong, and Leonidas Stamatatos. Binding Interactions between Soluble HIV Envelope Glycoproteins and Quaternary-Structure-Specific Monoclonal Antibodies PG9 and PG16. J. Virol., 85(14):7095-7107, Jul 2011. PubMed ID: 21543501. Show all entries for this paper.

Davis2009 Katie L. Davis, Frederic Bibollet-Ruche, Hui Li, Julie M. Decker, Olaf Kutsch, Lynn Morris, Aidy Salomon, Abraham Pinter, James A. Hoxie, Beatrice H. Hahn, Peter D. Kwong, and George M. Shaw. Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma. J. Virol., 83(3):1240-1259, Feb 2009. PubMed ID: 19019969. Show all entries for this paper.

Derby2006 Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322. Show all entries for this paper.

Derby2007 Nina R. Derby, Sean Gray, Elizabeth Wayner, Dwayne Campogan, Giorgos Vlahogiannis, Zane Kraft, Susan W. Barnett, Indresh K. Srivastava, and Leonidas Stamatatos. Isolation and Characterization of Monoclonal Antibodies Elicited by Trimeric HIV-1 Env gp140 Protein Immunogens. Virology, 366(2):433-445, 30 Sep 2007. PubMed ID: 17560621. Show all entries for this paper.

Dervillez2010 Xavier Dervillez, Volker Klaukien, Ralf Dürr, Joachim Koch, Alexandra Kreutz, Thomas Haarmann, Michaela Stoll, Donghan Lee, Teresa Carlomagno, Barbara Schnierle, Kalle Möbius, Christoph Königs, Christian Griesinger, and Ursula Dietrich. Peptide Ligands Selected with CD4-Induced Epitopes on Native Dualtropic HIV-1 Envelope Proteins Mimic Extracellular Coreceptor Domains and Bind to HIV-1 gp120 Independently of Coreceptor Usage. J. Virol., 84(19):10131-10138, Oct 2010. PubMed ID: 20660187. Show all entries for this paper.

Dey2008 Antu K. Dey, Kathryn B. David, Neelanjana Ray, Thomas J. Ketas, Per J. Klasse, Robert W. Doms, and John P. Moore. N-Terminal Substitutions in HIV-1 gp41 Reduce the Expression of Non-Trimeric Envelope Glycoproteins on the Virus. Virology, 372(1):187-200, 1 Mar 2008. PubMed ID: 18031785. Show all entries for this paper.

Dhillon2007 Amandeep K. Dhillon, Helen Donners, Ralph Pantophlet, Welkin E. Johnson, Julie M. Decker, George M. Shaw, Fang-Hua Lee, Douglas D. Richman, Robert W. Doms, Guido Vanham, and Dennis R. Burton. Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors. J. Virol., 81(12):6548-6562, Jun 2007. PubMed ID: 17409160. Show all entries for this paper.

Dhillon2008 Amandeep K. Dhillon, Robyn L. Stanfield, Miroslaw K. Gorny, Constance Williams, Susan Zolla-Pazner, and Ian A. Wilson. Structure Determination of an Anti-HIV-1 Fab 447-52D-Peptide Complex from an Epitaxially Twinned Data Set. Acta. Crystallogr. D Biol. Crystallogr., D64(7):792-802, Jul 2008. PubMed ID: 18566514. Show all entries for this paper.

Doria-Rose2010 Nicole A. Doria-Rose, Rachel M. Klein, Marcus G. Daniels, Sijy O'Dell, Martha Nason, Alan Lapedes, Tanmoy Bhattacharya, Stephen A. Migueles, Richard T. Wyatt, Bette T. Korber, John R. Mascola, and Mark Connors. Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables. J. Virol., 84(3):1631-1636, Feb 2010. PubMed ID: 19923174. Show all entries for this paper.

Douagi2010 Iyadh Douagi, Mattias N. E. Forsell, Christopher Sundling, Sijy O'Dell, Yu Feng, Pia Dosenovic, Yuxing Li, Robert Seder, Karin Loré, John R. Mascola, Richard T. Wyatt, and Gunilla B. Karlsson Hedestam. Influence of Novel CD4 Binding-Defective HIV-1 Envelope Glycoprotein Immunogens on Neutralizing Antibody and T-Cell Responses in Nonhuman Primates. J. Virol., 84(4):1683-1695, Feb 2010. PubMed ID: 19955308. Show all entries for this paper.

Eda2006 Yasuyuki Eda, Toshio Murakami, Yasushi Ami, Tadashi Nakasone, Mari Takizawa, Kenji Someya, Masahiko Kaizu, Yasuyuki Izumi, Naoto Yoshino, Shuzo Matsushita, Hirofumi Higuchi, Hajime Matsui, Katsuaki Shinohara, Hiroaki Takeuchi, Yoshio Koyanagi, Naoki Yamamoto, and Mitsuo Honda. Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection. J. Virol., 80(11):5563-5570, Jun 2006. PubMed ID: 16699037. Show all entries for this paper.

Eda2006a Yasuyuki Eda, Mari Takizawa, Toshio Murakami, Hiroaki Maeda, Kazuhiko Kimachi, Hiroshi Yonemura, Satoshi Koyanagi, Kouichi Shiosaki, Hirofumi Higuchi, Keiichi Makizumi, Toshihiro Nakashima, Kiyoshi Osatomi, Sachio Tokiyoshi, Shuzo Matsushita, Naoki Yamamoto, and Mitsuo Honda. Sequential Immunization with V3 Peptides from Primary Human Immunodeficiency Virus Type 1 Produces Cross-Neutralizing Antibodies against Primary Isolates with a Matching Narrow-Neutralization Sequence Motif. J. Virol., 80(11):5552-5562, Jun 2006. PubMed ID: 16699036. Show all entries for this paper.

Fenyo2009 Eva Maria Fenyö, Alan Heath, Stefania Dispinseri, Harvey Holmes, Paolo Lusso, Susan Zolla-Pazner, Helen Donners, Leo Heyndrickx, Jose Alcami, Vera Bongertz, Christian Jassoy, Mauro Malnati, David Montefiori, Christiane Moog, Lynn Morris, Saladin Osmanov, Victoria Polonis, Quentin Sattentau, Hanneke Schuitemaker, Ruengpung Sutthent, Terri Wrin, and Gabriella Scarlatti. International Network for Comparison of HIV Neutralization Assays: The NeutNet Report. PLoS One, 4(2):e4505, 2009. PubMed ID: 19229336. Show all entries for this paper.

Ferrantelli2002 Flavia Ferrantelli and Ruth M. Ruprecht. Neutralizing Antibodies Against HIV --- Back in the Major Leagues? Curr. Opin. Immunol., 14(4):495-502, Aug 2002. PubMed ID: 12088685. Show all entries for this paper.

Forsell2008 Mattias N. E. Forsell, Barna Dey, Andreas Mörner, Krisha Svehla, Sijy O'dell, Carl-Magnus Högerkorp, Gerald Voss, Rigmor Thorstensson, George M. Shaw, John R. Mascola, Gunilla B. Karlsson Hedestam, and Richard T. Wyatt. B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4. PLoS Pathog., 4(10):e1000171, 2008. PubMed ID: 18833294. Show all entries for this paper.

Forsman2008 Anna Forsman, Els Beirnaert, Marlén M. I. Aasa-Chapman, Bart Hoorelbeke, Karolin Hijazi, Willie Koh, Vanessa Tack, Agnieszka Szynol, Charles Kelly, Áine McKnight, Theo Verrips, Hans de Haard, and Robin A Weiss. Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120. J. Virol., 82(24):12069-12081, Dec 2008. PubMed ID: 18842738. Show all entries for this paper.

Forthal1995 D. N. Forthal, G. Landucci, M. K. Gorny, S. Zolla-Pazner, and W. E. Robinson, Jr. Functional Activities of 20 Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 11:1095-1099, 1995. A series of tests were performed on 20 human monoclonal antibodies to assess their potential therapeutic utility. Antibodies were tested for potentially harmful complement-mediated antibody enhancing activity (C-ADE), and for potentially beneficial neutralizing activity and antibody dependent cellular cytotoxicity ADCC. PubMed ID: 8554906. Show all entries for this paper.

Forthal2009 Donald N. Forthal and Christiane Moog. Fc Receptor-Mediated Antiviral Antibodies. Curr. Opin. HIV AIDS, 4(5):388-393, Sep 2009. PubMed ID: 20048702. Show all entries for this paper.

Gao2005a Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, and Barton F. Haynes. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein. J. Virol., 79(2):1154-1163, Jan 2005. PubMed ID: 15613343. Show all entries for this paper.

Gazarian2013 Karlen G. Gazarian, Yadira Palacios-Rodríguez, Tatiana G. Gazarian, and Leonor Huerta. HIV-1 V3 Loop Crown Epitope-Focused Mimotope Selection by Patient Serum from Random Phage Display Libraries: Implications for the Epitope Structural Features. Mol. Immunol., 54(2):148-156, Jun 2013. PubMed ID: 23270686. Show all entries for this paper.

Gonzalez2010 Nuria Gonzalez, Amparo Alvarez, and Jose Alcami. Broadly Neutralizing Antibodies and their Significance for HIV-1 Vaccines. Curr. HIV Res., 8(8):602-612, Dec 2010. PubMed ID: 21054253. Show all entries for this paper.

Gorny1992 M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner. Neutralization of Diverse Human Immunodeficiency Virus Type 1 Variants by an Anti-V3 Human Monoclonal Antibody. J. Virol., 66:7538-7542, 1992. PubMed ID: 1433529. Show all entries for this paper.

Gorny1993 M. K. Gorny, J.-Y. Xu, S. Karwowska, A. Buchbinder, and S. Zolla-Pazner. Repertoire of Neutralizing Human Monoclonal Antibodies Specific for The V3 Domain of HIV-1 gp120. J. Immunol., 150:635-643, 1993. Characterizaton of 12 human MAbs that bind and neutralize the MN isolate with 50\% neutralization. Two of these antibodies also bound and neutralized IIIB: 447-52-D and 694/98-D; all others could not bind HXB2 peptides. All but two, 418-D and 412-D could bind to SF2 peptides. PubMed ID: 7678279. Show all entries for this paper.

Gorny1994 M. K. Gorny, J. P. Moore, A. J. Conley, S. Karwowska, J. Sodroski, C. Williams, S. Burda, L. J. Boots, and S. Zolla-Pazner. Human Anti-V2 Monoclonal Antibody That Neutralizes Primary but Not Laboratory Isolates of Human Immunodeficiency Virus Type 1. J. Virol., 68:8312-8320, 1994. Detailed characterization of the MAb 697-D. PubMed ID: 7525987. Show all entries for this paper.

Gorny1997 Miroslaw K. Gorny, Thomas C. VanCott, Catarina Hioe, Zimra R. Israel, Nelson L. Michael, Anthony J. Conley, Constance Williams, Joseph A. Kessler II, Padmasree Chigurupati, Sherri Burda, and Susan Zolla-Pazner. Human Monoclonal Antibodies to the V3 Loop of HIV-1 With Intra- and Interclade Cross-Reactivity. J. Immunol., 159:5114-5122, 1997. PubMed ID: 9366441. Show all entries for this paper.

Gorny1998 M. K. Gorny, J. R. Mascola, Z. R. Israel, T. C. VanCott, C. Williams, P. Balfe, C. Hioe, S. Brodine, S. Burda, and S. Zolla-Pazner. A Human Monoclonal Antibody Specific for the V3 Loop of HIV Type 1 Clade E Cross-Reacts with Other HIV Type 1 Clades. AIDS Res. Hum. Retroviruses, 14:213-221, 1998. PubMed ID: 9491911. Show all entries for this paper.

Gorny2000b M. K. Gorny, T. C. VanCott, C. Williams, K. Revesz, and S. Zolla-Pazner. Effects of oligomerization on the epitopes of the human immunodeficiency virus type 1 envelope glycoproteins. Virology, 267:220-8, 2000. PubMed ID: 10662617. Show all entries for this paper.

Gorny2002 Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Sandra Cohen, Victoria R. Polonis, William J. Honnen, Samuel C. Kayman, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades. J. Virol., 76(18):9035-9045, Sep 2002. PubMed ID: 12186887. Show all entries for this paper.

Gorny2004 Miroslaw K. Gorny, Kathy Revesz, Constance Williams, Barbara Volsky, Mark K. Louder, Christopher A. Anyangwe, Chavdar Krachmarov, Samuel C. Kayman, Abraham Pinter, Arthur Nadas, Phillipe N. Nyambi, John R. Mascola, and Susan Zolla-Pazner. The V3 Loop is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope. J. Virol., 78(5):2394-2404, Mar 2004. PubMed ID: 14963135. Show all entries for this paper.

Gorny2005 Miroslaw K. Gorny, Leonidas Stamatatos, Barbara Volsky, Kathy Revesz, Constance Williams, Xiao-Hong Wang, Sandra Cohen, Robert Staudinger, and Susan Zolla-Pazner. Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles. J. Virol., 79(8):5232-5237, Apr 2005. PubMed ID: 15795308. Show all entries for this paper.

Gorny2006 Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Xiao-Hong Wang, Sherri Burda, Tetsuya Kimura, Frank A. J. Konings, Arthur Nádas, Christopher A. Anyangwe, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):6865-6872, Jul 2006. PubMed ID: 16809292. Show all entries for this paper.

Gorny2009 Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295. Show all entries for this paper.

Grovit-Ferbas2000 K. Grovit-Ferbas, J. F. Hsu, J. Ferbas, V. Gudeman, and I. S. Chen. Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1. J. Virol., 74(13):5802-9, Jul 2000. URL: http://jvi.asm.org/cgi/content/full/74/13/5802. PubMed ID: 10846059. Show all entries for this paper.

Grundner2005 Christoph Grundner, Yuxing Li, Mark Louder, John Mascola, Xinzhen Yang, Joseph Sodroski, and Richard Wyatt. Analysis of the Neutralizing Antibody Response Elicited in Rabbits by Repeated Inoculation with Trimeric HIV-1 Envelope Glycoproteins. Virology, 331(1):33-46, 5 Jan 2005. PubMed ID: 15582651. Show all entries for this paper.

Guzzo2018 Christina Guzzo, Peng Zhang, Qingbo Liu, Alice L. Kwon, Ferzan Uddin, Alexandra I. Wells, Hana Schmeisser, Raffaello Cimbro, Jinghe Huang, Nicole Doria-Rose, Stephen D. Schmidt, Michael A. Dolan, Mark Connors, John R. Mascola, and Paolo Lusso. Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation. mBio, 9(6), 11 Dec 2018. PubMed ID: 30538178. Show all entries for this paper.

Haldar2011 Bijayesh Haldar, Sherri Burda, Constance Williams, Leo Heyndrickx, Guido Vanham, Miroslaw K. Gorny, and Phillipe Nyambi. Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies. PLoS One, 6(2):e17253, 2011. PubMed ID: 21383841. Show all entries for this paper.

Haynes2005 Barton F. Haynes, Judith Fleming, E. William St. Clair, Herman Katinger, Gabriela Stiegler, Renate Kunert, James Robinson, Richard M. Scearce, Kelly Plonk, Herman F. Staats, Thomas L. Ortel, Hua-Xin Liao, and S. Munir Alam. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. Science, 308(5730):1906-1908, 24 Jun 2005. Comment in Science 2005 Jun 24;308(5730):1878-9. PubMed ID: 15860590. Show all entries for this paper.

Haynes2006 Barton F. Haynes, Benjiang Ma, David C. Montefiori, Terri Wrin, Christos J. Petropoulos, Laura L. Sutherland, Richard M. Scearce, Cathrine. Denton, Shi-Mao Xia, Bette T. Korber, and Hua-Xin Liao. Analysis of HIV-1 Subtype B Third Variable Region Peptide Motifs for Induction of Neutralizing Antibodies against HIV-1 Primary Isolates. Virology, 345(1):44-55, 5 Feb 2006. PubMed ID: 16242749. Show all entries for this paper.

Haynes2006a Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638. Show all entries for this paper.

He2002 Yuxian He, William J. Honnen, Chavdar P. Krachmarov, Michael Burkhart, Samuel C. Kayman, Jose Corvalan, and Abraham Pinter. Efficient Isolation of Novel Human Monoclonal Antibodies with Neutralizing Activity Against HIV-1 from Transgenic Mice Expressing Human Ig Loci. J. Immunol., 169(1):595-605, 1 Jul 2002. PubMed ID: 12077293. Show all entries for this paper.

Hill1997 C. M. Hill, H. Deng, D. Unutmaz, V. N. Kewalramani, L. Bastiani, M. K. Gorny, S. Zolla-Pazner, and D. R. Littman. Envelope glycoproteins from human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus can use human CCR5 as a coreceptor for viral entry and make direct CD4-dependent interactions with this chemokine receptor. J. Virol., 71:6296-6304, 1997. PubMed ID: 9261346. Show all entries for this paper.

Hioe1997 C. Hioe, S. Burda, P. Chigurupati, S. Xu, and S. Zolla-Pazner. Resting Cell Neutralization Assay for HIV-1 Primary Isolates. Methods: A companion to Methods in Enzymology, 12:300-305, 1997. A technique is described for detecting the activity of neutralizing polyclonal or MAbs against HIV-1 primary isolates, using unstimulated PBMC as the target cell. PubMed ID: 9245610. Show all entries for this paper.

Hioe1997b C. E. Hioe, S. Xu, P. Chigurupati, S. Burda, C. Williams, M. K. Gorny, and S. Zolla-Pazner. Neutralization of HIV-1 Primary Isolates by Polyclonal and Monoclonal Human Antibodies. Int. Immunol., 9(9):1281-1290, Sep 1997. PubMed ID: 9310831. Show all entries for this paper.

Hioe1999 C. E. Hioe, J. E. Hildreth, and S. Zolla-Pazner. Enhanced HIV Type 1 Neutralization by Human Anti-Glycoprotein 120 Monoclonal Antibodies in the Presence of Monoclonal Antibodies to Lymphocyte Function-Associated Molecule 1. AIDS Res. Hum. Retroviruses, 15:523-531, 1999. PubMed ID: 10221529. Show all entries for this paper.

Hioe2000 C. E. Hioe, G. J. Jones, A. D. Rees, S. Ratto-Kim, D. Birx, C. Munz, M. K. Gorny, M. Tuen, and S. Zolla-Pazner. Anti-CD4-Binding Domain Antibodies Complexed with HIV Type 1 Glycoprotein 120 Inhibit CD4+ T Cell-Proliferative Responses to Glycoprotein 120. AIDS Res. Hum. Retroviruses, 16:893-905, 2000. PubMed ID: 10875615. Show all entries for this paper.

Hioe2009 Catarina E. Hioe, Maria Luisa Visciano, Rajnish Kumar, Jianping Liu, Ethan A. Mack, Rachel E. Simon, David N. Levy, and Michael Tuen. The Use of Immune Complex Vaccines to Enhance Antibody Responses against Neutralizing Epitopes on HIV-1 Envelope gp120. Vaccine, 28(2):352-360, 11 Dec 2009. PubMed ID: 19879224. Show all entries for this paper.

Hioe2010 Catarina E. Hioe, Terri Wrin, Michael S. Seaman, Xuesong Yu, Blake Wood, Steve Self, Constance Williams, Miroslaw K. Gorny, and Susan Zolla-Pazner. Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes. PLoS One, 5(4):e10254, 2010. PubMed ID: 20421997. Show all entries for this paper.

Hogan2018 Michael J. Hogan, Angela Conde-Motter, Andrea P. O. Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C. LaBranche, David C. Montefiori, Shiu-Lok Hu, James A. Hoxie, and Drew Weissman. Increased Surface Expression of HIV-1 Envelope Is Associated with Improved Antibody Response in Vaccinia Prime/Protein Boost Immunization. Virology, 514:106-117, 15 Jan 2018. PubMed ID: 29175625. Show all entries for this paper.

Holl2006 Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957. Show all entries for this paper.

Holl2006a Vincent Holl, Maryse Peressin, Sylvie Schmidt, Thomas Decoville, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Efficient Inhibition of HIV-1 Replication in Human Immature Monocyte-Derived Dendritic Cells by Purified Anti-HIV-1 IgG without Induction of Maturation. Blood, 107(11):4466-4474, 1 Jun 2006. PubMed ID: 16469871. Show all entries for this paper.

Hoxie2010 James A. Hoxie. Toward an Antibody-Based HIV-1 Vaccine. Annu. Rev. Med., 61:135-52, 2010. PubMed ID: 19824826. Show all entries for this paper.

Hu2007 Qinxue Hu, Naheed Mahmood, and Robin J. Shattock. High-Mannose-Specific Deglycosylation of HIV-1 gp120 Induced by Resistance to Cyanovirin-N and the Impact on Antibody Neutralization. Virology, 368(1):145-154, 10 Nov 2007. PubMed ID: 17658575. Show all entries for this paper.

Huang2010 Kuan-Hsiang G. Huang, David Bonsall, Aris Katzourakis, Emma C. Thomson, Sarah J. Fidler, Janice Main, David Muir, Jonathan N. Weber, Alexander J. Frater, Rodney E. Phillips, Oliver G. Pybus, Philip J. R. Goulder, Myra O. McClure, Graham S. Cooke, and Paul Klenerman. B-Cell Depletion Reveals a Role for Antibodies in the Control of Chronic HIV-1 Infection. Nat. Commun., 1:102, 2010. PubMed ID: 20981030. Show all entries for this paper.

Huber2007 M. Huber and A. Trkola. Humoral Immunity to HIV-1: Neutralization and Beyond. J. Intern. Med., 262(1):5-25, Jul 2007. PubMed ID: 17598812. Show all entries for this paper.

Inouye1998 P. Inouye, E. Cherry, M. Hsu, S. Zolla-Pazner, and M. A. Wainberg. Neutralizing Antibodies Directed against the V3 Loop Select for Different Escape Variants in a Virus with Mutated Reverse Transcriptase (M184V) Than in Wild-Type Human Immunodeficiency Virus Type 1. AIDS Res. Hum. Retroviruses, 14:735-740, 1998. The M184V substitution in RT yields high level resistance to 3TC and low level resistance to ddI and ddC, and alters the properties of RT. Virus containing the wt form of RT grown in the presence of the MAb 447-D develops 447-D resistance in 36 days, with the GPGR to GPGK substitutions (AGA(R) to AAA(K)). 447-D resistance took longer to acquire in virus with the M184V substituted RT, and had the form CTRPN to CTRPY (AAC(N) to TAC(Y)) at position 5 of the V3 loop. PubMed ID: 9643373. Show all entries for this paper.

Jagodzinski1996 P. P. Jagodzinski, J. Wustner, D. Kmieciak, T. J. Wasik, A. Fertala, A. L. Sieron, M. Takahashi, T. Tsuji, T. Mimura, M. S. Fung, M. K. Gorny, M. Kloczewiak, Y. Kaneko, and D. Kozbor. Role of the V2, V3, and CD4-Binding Domains of GP120 in Curdlan Sulfate Neutralization Sensitivity of HIV-1 during Infection of T Lymphocytes. Virology, 226:217-227, 1996. PubMed ID: 8955041. Show all entries for this paper.

Jiang2010 Xunqing Jiang, Valicia Burke, Maxim Totrov, Constance Williams, Timothy Cardozo, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Conserved Structural Elements in the V3 Crown of HIV-1 gp120. Nat. Struct. Mol. Biol., 17(8):955-961, Aug 2010. PubMed ID: 20622876. Show all entries for this paper.

Kang2005 Sang-Moo Kang, Fu Shi Quan, Chunzi Huang, Lizheng Guo, Ling Ye, Chinglai Yang, and Richard W. Compans. Modified HIV Envelope Proteins with Enhanced Binding to Neutralizing Monoclonal Antibodies. Virology, 331(1):20-32, 5 Jan 2005. PubMed ID: 15582650. Show all entries for this paper.

Karwowska1992a S. Karwowska, M. K. Gorny, A. Buchbinder, and S. Zolla-Pazner. Type-specific human monoclonal antibodies cross-react with the V3-loop of various HIV-1 isolates. Vaccines 92, :171-174, 1992. Editors: F. Brown, H. S. Ginsberg and R. Lerner, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Show all entries for this paper.

Keele2008 Brandon F. Keele, Elena E. Giorgi, Jesus F. Salazar-Gonzalez, Julie M. Decker, Kimmy T. Pham, Maria G. Salazar, Chuanxi Sun, Truman Grayson, Shuyi Wang, Hui Li, Xiping Wei, Chunlai Jiang, Jennifer L. Kirchherr, Feng Gao, Jeffery A. Anderson, Li-Hua Ping, Ronald Swanstrom, Georgia D. Tomaras, William A. Blattner, Paul A. Goepfert, J. Michael Kilby, Michael S. Saag, Eric L. Delwart, Michael P. Busch, Myron S. Cohen, David C. Montefiori, Barton F. Haynes, Brian Gaschen, Gayathri S. Athreya, Ha Y. Lee, Natasha Wood, Cathal Seoighe, Alan S. Perelson, Tanmoy Bhattacharya, Bette T. Korber, Beatrice H. Hahn, and George M. Shaw. Identification and Characterization of Transmitted and Early Founder Virus Envelopes in Primary HIV-1 Infection. Proc. Natl. Acad. Sci. U.S.A., 105(21):7552-7557, 27 May 2008. PubMed ID: 18490657. Show all entries for this paper.

Keller1993 P. M. Keller, B. A. Arnold, A. R. Shaw, R. L. Tolman, F. Van Middlesworth, S. Bondy, V. K. Rusiecki, S. Koenig, S. Zolla-Pazner, P. Conard, E. A. Emini, and A. J. Conley. Identification of HIV Vaccine Candidate Peptides by Screening Random Phage Epitope Libraries. Virology, 193:709-716, 1993. A library of 15 mers was screened for reactivity with 447-52D. 100s of 15 mers reacted, of which 70 were sequenced. All but one contained the motif GPXR. PubMed ID: 7681612. Show all entries for this paper.

Kessler2003 Naama Kessler, Anat Zvi, Min Ji, Michal Sharon, Osnat Rosen, Rina Levy, Miroslaw Gorny, Suzan Zolla-Pazner, and Jacob Anglister. Expression, Purification, and Isotope Labeling of the Fv of the Human HIV-1 Neutralizing Antibody 447-52D for NMR Studies. Protein. Expr. Purif., 29(2):291-303, Jun 2003. PubMed ID: 12767822. Show all entries for this paper.

Kimura2009 Tetsuya Kimura, Xiao-Hong Wang, Constance Williams, Susan Zolla-Pazner, and Miroslaw K. Gorny. Human Monoclonal Antibody 2909 Binds to Pseudovirions Expressing Trimers but not Monomeric HIV-1 Envelope Proteins. Hum. Antibodies, 18(1-2):35-40, 2009. PubMed ID: 19478397. Show all entries for this paper.

Klein2013 Florian Klein, Ron Diskin, Johannes F. Scheid, Christian Gaebler, Hugo Mouquet, Ivelin S. Georgiev, Marie Pancera, Tongqing Zhou, Reha-Baris Incesu, Brooks Zhongzheng Fu, Priyanthi N. P. Gnanapragasam, Thiago Y. Oliveira, Michael S. Seaman, Peter D. Kwong, Pamela J. Bjorkman, and Michel C. Nussenzweig. Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization. Cell, 153(1):126-138, 28 Mar 2013. PubMed ID: 23540694. Show all entries for this paper.

Korber2009 Bette Korber and S. Gnanakaran. The Implications of Patterns in HIV Diversity for Neutralizing Antibody Induction and Susceptibility. Curr. Opin. HIV AIDS, 4(5):408-417, Sep 2009. PubMed ID: 20048705. Show all entries for this paper.

Krachmarov2005 Chavdar Krachmarov, Abraham Pinter, William J. Honnen, Miroslaw K. Gorny, Phillipe N. Nyambi, Susan Zolla-Pazner, and Samuel C. Kayman. Antibodies That Are Cross-Reactive for Human Immunodeficiency Virus Type 1 Clade A and Clade B V3 Domains Are Common in Patient Sera from Cameroon, but Their Neutralization Activity Is Usually Restricted by Epitope Masking. J. Virol., 79(2):780-790, Jan 2005. PubMed ID: 15613306. Show all entries for this paper.

Krachmarov2006 C. P. Krachmarov, W. J. Honnen, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and Abraham Pinter. Factors Determining the Breadth and Potency of Neutralization by V3-Specific Human Monoclonal Antibodies Derived from Subjects Infected with Clade A or Clade B Strains of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):7127-7135, Jul 2006. PubMed ID: 16809318. Show all entries for this paper.

Kraft2007 Zane Kraft, Nina R. Derby, Ruth A. McCaffrey, Rachel Niec, Wendy M. Blay, Nancy L. Haigwood, Eirini Moysi, Cheryl J. Saunders, Terri Wrin, Christos J. Petropoulos, M. Juliana McElrath, and Leonidas Stamatatos. Macaques Infected with a CCR5-Tropic Simian/Human Immunodeficiency Virus (SHIV) Develop Broadly Reactive Anti-HIV Neutralizing Antibodies. J. Virol., 81(12):6402-6411, Jun 2007. PubMed ID: 17392364. Show all entries for this paper.

Kwong2009a Peter D. Kwong and Ian A. Wilson. HIV-1 and Influenza Antibodies: Seeing Antigens in New Ways. Nat. Immunol., 10(6):573-578, Jun 2009. PubMed ID: 19448659. Show all entries for this paper.

Laal1994 Suman Laal, Sherri Burda, Miroslav K. Gorny, Sylwia Karwowska, Aby Buchbinder, and Susan Zolla-Pazner. Synergistic Neutralization of Human Immunodeficiency Virus Type 1 by Combinations of Human Monoclonal Antibodies. J. Virol., 68(6):4001-4008, Jun 1994. PubMed ID: 7514683. Show all entries for this paper.

Law2007 Mansun Law, Rosa M. F. Cardoso, Ian A. Wilson, and Dennis R. Burton. Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy. J. Virol., 81(8):4272-4285, Apr 2007. PubMed ID: 17267498. Show all entries for this paper.

Lewis1995 C. M. Lewis, G. F. Hollis, G. E. Mark, 3rd, J. S. Tung, and S. W. Ludmerer. Use of a Novel Mutagenesis Strategy, Optimized Residue Substitution, to Decrease the Off-Rate of an Anti-gp120 Antibody. Mol. Immunol., 32(14-15):1065-1072, Oct 1995. PubMed ID: 8544856. Show all entries for this paper.

Li2005a Ming Li, Feng Gao, John R. Mascola, Leonidas Stamatatos, Victoria R. Polonis, Marguerite Koutsoukos, Gerald Voss, Paul Goepfert, Peter Gilbert, Kelli M. Greene, Miroslawa Bilska, Denise L Kothe, Jesus F. Salazar-Gonzalez, Xiping Wei, Julie M. Decker, Beatrice H. Hahn, and David C. Montefiori. Human Immunodeficiency Virus Type 1 env Clones from Acute and Early Subtype B Infections for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies. J. Virol., 79(16):10108-10125, Aug 2005. PubMed ID: 16051804. Show all entries for this paper.

Li2007a Yuxing Li, Stephen A. Migueles, Brent Welcher, Krisha Svehla, Adhuna Phogat, Mark K. Louder, Xueling Wu, George M. Shaw, Mark Connors, Richard T. Wyatt, and John R. Mascola. Broad HIV-1 Neutralization Mediated by CD4-Binding Site Antibodies. Nat. Med., 13(9):1032-1034, Sep 2007. PubMed ID: 17721546. Show all entries for this paper.

Li2009c Yuxing Li, Krisha Svehla, Mark K. Louder, Diane Wycuff, Sanjay Phogat, Min Tang, Stephen A. Migueles, Xueling Wu, Adhuna Phogat, George M. Shaw, Mark Connors, James Hoxie, John R. Mascola, and Richard Wyatt. Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals. J Virol, 83(2):1045-1059, Jan 2009. PubMed ID: 19004942. Show all entries for this paper.

Lin2007 George Lin and Peter L. Nara. Designing Immunogens to Elicit Broadly Neutralizing Antibodies to the HIV-1 Envelope Glycoprotein. Curr. HIV Res., 5(6):514-541, Nov 2007. PubMed ID: 18045109. Show all entries for this paper.

Ling2004 Hong Ling, Peng Xiao, Osamu Usami, and Toshio Hattori. Thrombin Activates Envelope Glycoproteins of HIV Type 1 and Enhances Fusion. Microbes Infect., 6(5):414-420, Apr 2004. PubMed ID: 15109955. Show all entries for this paper.

Louder2005 Mark K. Louder, Anna Sambor, Elena Chertova, Tai Hunte, Sarah Barrett, Fallon Ojong, Eric Sanders-Buell, Susan Zolla-Pazner, Francine E. McCutchan, James D. Roser, Dana Gabuzda, Jeffrey D. Lifson, and John R. Mascola. HIV-1 Envelope Pseudotyped Viral Vectors and Infectious Molecular Clones Expressing the Same Envelope Glycoprotein Have a Similar Neutralization Phenotype, but Culture in Peripheral Blood Mononuclear Cells Is Associated with Decreased Neutralization Sensitivity. Virology, 339(2):226-238, 1 Sep 2005. PubMed ID: 16005039. Show all entries for this paper.

Lusso2005 Paolo Lusso, Patricia L. Earl, Francesca Sironi, Fabio Santoro, Chiara Ripamonti, Gabriella Scarlatti, Renato Longhi, Edward A. Berger, and Samuele E. Burastero. Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains. J. Virol., 79(11):6957-6968, Jun 2005. PubMed ID: 15890935. Show all entries for this paper.

Ly2000 A. Ly and L. Stamatatos. V2 Loop Glycosylation of the Human Immunodeficiency Virus Type 1 SF162 Envelope Facilitates Interaction of this Protein with CD4 and CCR5 Receptors and Protects the Virus from Neutralization by Anti-V3 Loop and Anti-CD4 Binding Site Antibodies. J. Virol., 74:6769-6776, 2000. PubMed ID: 10888615. Show all entries for this paper.

Martin2008 Grégoire Martin, Yide Sun, Bernadette Heyd, Olivier Combes, Jeffrey B Ulmer, Anne Descours, Susan W Barnett, Indresh K Srivastava, and Loïc Martin. A Simple One-Step Method for the Preparation of HIV-1 Envelope Glycoprotein Immunogens Based on a CD4 Mimic Peptide. Virology, 381(2):241-250, 25 Nov 2008. PubMed ID: 18835005. Show all entries for this paper.

Martin2011 Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B. Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W. Barnett, Indresh K. Srivastava, Pascal Kessler, and Loïc Martin. Stabilization of HIV-1 Envelope in the CD4-Bound Conformation through Specific Cross-Linking of a CD4 Mimetic. J. Biol. Chem., 286(24):21706-21716, 17 Jun 2011. PubMed ID: 21487012. Show all entries for this paper.

Martin-Garcia2005 Julio Martín-García, Simon Cocklin, Irwin M. Chaiken, and Francisco González-Scarano. Interaction with CD4 and Antibodies to CD4-Induced Epitopes of the Envelope gp120 from a Microglial Cell-Adapted Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 79(11):6703-6713, Jun 2005. PubMed ID: 15890908. Show all entries for this paper.

McCaffrey2004 Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849. Show all entries for this paper.

McGuire2014 Andrew T. McGuire, Jolene A. Glenn, Adriana Lippy, and Leonidas Stamatatos. Diverse Recombinant HIV-1 Envs Fail to Activate B Cells Expressing the Germline B Cell Receptors of the Broadly Neutralizing Anti-HIV-1 Antibodies PG9 and 447-52D. J. Virol., 88(5):2645-2657, Mar 2014. PubMed ID: 24352455. Show all entries for this paper.

McKnight2007 Aine McKnight and Marlen M. I. Aasa-Chapman. Clade Specific Neutralising Vaccines for HIV: An Appropriate Target? Curr. HIV Res., 5(6):554-560, Nov 2007. PubMed ID: 18045111. Show all entries for this paper.

Mester2009 Brenda Mester, Revital Manor, Amit Mor, Boris Arshava, Osnat Rosen, Fa-Xiang Ding, Fred Naider, and Jacob Anglister. HIV-1 Peptide Vaccine Candidates: Selecting Constrained V3 Peptides with Highest Affinity to Antibody 447-52D. Biochemistry, 48(33):7867-7877, 25 Aug 2009. PubMed ID: 19552398. Show all entries for this paper.

Moore2006 Penny L. Moore, Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, Michael B. Zwick, Michael Franti, Lynn Morris, Kenneth H. Roux, Dennis R. Burton, and James M. Binley. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1. J. Virol., 80(5):2515-2528, Mar 2006. PubMed ID: 16474158. Show all entries for this paper.

Mor2009 Amit Mor, Eugenia Segal, Brenda Mester, Boris Arshava, Osnat Rosen, Fa-Xiang Ding, Joseph Russo, Amnon Dafni, Fabian Schvartzman, Tali Scherf, Fred Naider, and Jacob Anglister. Mimicking the Structure of the V3 Epitope Bound to HIV-1 Neutralizing Antibodies. Biochemistry, 48(15):3288-3303, 21 Apr 2009. PubMed ID: 19281264. Show all entries for this paper.

Musich2011 Thomas Musich, Paul J. Peters, Maria José Duenas-Decamp, Maria Paz Gonzalez-Perez, James Robinson, Susan Zolla-Pazner, Jonathan K. Ball, Katherine Luzuriaga, and Paul R. Clapham. A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop to Prime Low CD4 Use and Macrophage Infection. J. Virol., 85(5):2397-2405, Mar 2011. PubMed ID: 21159865. Show all entries for this paper.

Nelson2007 Josh D. Nelson, Florence M. Brunel, Richard Jensen, Emma T. Crooks, Rosa M. F. Cardoso, Meng Wang, Ann Hessell, Ian A. Wilson, James M. Binley, Philip E. Dawson, Dennis R. Burton, and Michael B. Zwick. An Affinity-Enhanced Neutralizing Antibody against the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 Recognizes an Epitope between Those of 2F5 and 4E10. J. Virol., 81(8):4033-4043, Apr 2007. PubMed ID: 17287272. Show all entries for this paper.

Nishiyama2009 Yasuhiro Nishiyama, Stephanie Planque, Yukie Mitsuda, Giovanni Nitti, Hiroaki Taguchi, Lei Jin, Jindrich Symersky, Stephane Boivin, Marcin Sienczyk, Maria Salas, Carl V. Hanson, and Sudhir Paul. Toward Effective HIV Vaccination: Induction of Binary Epitope Reactive Antibodies with Broad HIV Neutralizing Activity. J. Biol. Chem., 284(44):30627-30642, 30 Oct 2009. PubMed ID: 19726674. Show all entries for this paper.

Nyambi1998 P. N. Nyambi, M. K. Gorny, L. Bastiani, G. van der Groen, C. Williams, and S. Zolla-Pazner. Mapping of Epitopes Exposed on Intact Human Immunodeficiency Virus Type 1 (HIV-1) Virions: A New Strategy for Studying the Immunologic Relatedness of HIV-1. J. Virol., 72:9384-9391, 1998. 18 human MAbs binding to gp120 and gp41 were tested using a novel assay to test binding to intact HIV-1 virions. The new method involves using MAbs to the host proteins incorporated into virions to bind them to ELIZA plates. Antigenic conservation in epitopes of HIV-1 in clades A, B, D, F, G, and H was studied. MAbs were selected that were directed against V2, V3, CD4bd, C5 or gp41 regions. Antibodies against V2, the CD4BS, and sp41 showed weak and sporadic reactivities, while binding strongly to gp120, suggesting these epitopes are hidden when gp120 is in its native, quaternary structure. PubMed ID: 9765494. Show all entries for this paper.

Nyambi2000 P. N. Nyambi, H. A. Mbah, S. Burda, C. Williams, M. K. Gorny, A. Nadas, and S. Zolla-Pazner. Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M. J. Virol., 74:7096-7107, 2000. PubMed ID: 10888650. Show all entries for this paper.

ORourke2010 Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Dora P. A. J. Fonseca, Karianne Terry, Terri Wrin, Faruk Sinangil, and Phillip W. Berman. Mutation at a Single Position in the V2 Domain of the HIV-1 Envelope Protein Confers Neutralization Sensitivity to a Highly Neutralization-Resistant Virus. J. Virol., 84(21):11200-11209, Nov 2010. PubMed ID: 20702624. Show all entries for this paper.

Pantophlet2004 R. Pantophlet, I. A. Wilson, and D. R. Burton. Improved Design of an Antigen with Enhanced Specificity for the Broadly HIV-Neutralizing Antibody b12. Protein Eng. Des. Sel., 17(10):749-758, Oct 2004. PubMed ID: 15542540. Show all entries for this paper.

Pantophlet2006 Ralph Pantophlet and Dennis R. Burton. GP120: Target for Neutralizing HIV-1 Antibodies. Annu. Rev. Immunol., 24:739-769, 2006. PubMed ID: 16551265. Show all entries for this paper.

Pantophlet2007 Ralph Pantophlet, Rowena O. Aguilar-Sino, Terri Wrin, Lisa A. Cavacini, and Dennis R. Burton. Analysis of the Neutralization Breadth of the Anti-V3 Antibody F425-B4e8 and Re-assessment of its Epitope Fine Specificity by Scanning Mutagenesis. Virology, 364(2):441-453, 1 Aug 2007. PubMed ID: 17418361. Show all entries for this paper.

Pantophlet2010 Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886. Show all entries for this paper.

Peressin2011 M. Peressin, V. Holl, S. Schmidt, T. Decoville, D. Mirisky, A. Lederle, M. Delaporte, K. Xu, A. M. Aubertin, and C. Moog. HIV-1 Replication in Langerhans and Interstitial Dendritic Cells Is Inhibited by Neutralizing and Fc-Mediated Inhibitory Antibodies. J. Virol., 85(2):1077-1085, Jan 2011. PubMed ID: 21084491. Show all entries for this paper.

Phogat2007 S. Phogat, R. T. Wyatt, and G. B. Karlsson Hedestam. Inhibition of HIV-1 Entry by Antibodies: Potential Viral and Cellular Targets. J. Intern. Med., 262(1):26-43, Jul 2007. PubMed ID: 17598813. Show all entries for this paper.

Pinter2004 Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902. Show all entries for this paper.

Pinter2005 Abraham Pinter, William J. Honnen, Paul D'Agostino, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The C108g Epitope in the V2 Domain of gp120 Functions as a Potent Neutralization Target When Introduced into Envelope Proteins Derived from Human Immunodeficiency Virus Type 1 Primary Isolates. J. Virol., 79(11):6909-6917, Jun 2005. PubMed ID: 15890930. Show all entries for this paper.

Pugach2004 Pavel Pugach, Shawn E. Kuhmann, Joann Taylor, Andre J. Marozsan, Amy Snyder, Thomas Ketas, Steven M. Wolinsky, Bette T. Korber, and John P. Moore. The Prolonged Culture of Human Immunodeficiency Virus Type 1 in Primary Lymphocytes Increases its Sensitivity to Neutralization by Soluble CD4. Virology, 321(1):8-22, 30 Mar 2004. PubMed ID: 15033560. Show all entries for this paper.

Pugach2008 Pavel Pugach, Thomas J. Ketas, Elizabeth Michael, and John P. Moore. Neutralizing Antibody and Anti-Retroviral Drug Sensitivities of HIV-1 Isolates Resistant to Small Molecule CCR5 Inhibitors. Virology, 377(2):401-407, 1 Aug 2008. PubMed ID: 18519143. Show all entries for this paper.

Ringe2011 Rajesh Ringe, Deepak Sharma, Susan Zolla-Pazner, Sanjay Phogat, Arun Risbud, Madhuri Thakar, Ramesh Paranjape, and Jayanta Bhattacharya. A Single Amino Acid Substitution in the C4 Region in gp120 Confers Enhanced Neutralization of HIV-1 by Modulating CD4 Binding Sites and V3 Loop. Virology, 418(2):123-132, 30 Sep 2011. PubMed ID: 21851958. Show all entries for this paper.

Robinson2010 James E. Robinson, Kelly Franco, Debra Holton Elliott, Mary Jane Maher, Ashley Reyna, David C. Montefiori, Susan Zolla-Pazner, Miroslaw K. Gorny, Zane Kraft, and Leonidas Stamatatos. Quaternary Epitope Specificities of Anti-HIV-1 Neutralizing Antibodies Generated in Rhesus Macaques Infected by the Simian/Human Immunodeficiency Virus SHIVSF162P4. J. Virol., 84(7):3443-3453, Apr 2010. PubMed ID: 20106929. Show all entries for this paper.

Rosen2005 Osnat Rosen, Jordan Chill, Michal Sharon, Naama Kessler, Brenda Mester, Susan Zolla-Pazner, and Jacob Anglister. Induced Fit in HIV-Neutralizing Antibody Complexes: Evidence for Alternative Conformations of the gp120 V3 Loop and the Molecular Basis for Broad Neutralization. Biochemistry, 44(19):7250-7158, 17 May 2005. PubMed ID: 15882063. Show all entries for this paper.

Ruprecht2011 Claudia R. Ruprecht, Anders Krarup, Lucy Reynell, Axel M. Mann, Oliver F. Brandenberg, Livia Berlinger, Irene A. Abela, Roland R. Regoes, Huldrych F. Günthard, Peter Rusert, and Alexandra Trkola. MPER-Specific Antibodies Induce gp120 Shedding and Irreversibly Neutralize HIV-1. J. Exp. Med., 208(3):439-454, 14 Mar 2011. PubMed ID: 21357743. Show all entries for this paper.

Saarloos1995 M. N. Saarloos, T. F. Lint, and G. T. Spear. Efficacy of HIV-Specific and `Antibody-Independent' Mechanisms for Complement Activation by HIV-Infected Cells. Clin. Exp. Immunol., 99:189-195, 1995. PubMed ID: 7851010. Show all entries for this paper.

Sabin2010 Charles Sabin, Davide Corti, Victor Buzon, Mike S. Seaman, David Lutje Hulsik, Andreas Hinz, Fabrizia Vanzetta, Gloria Agatic, Chiara Silacci, Lara Mainetti, Gabriella Scarlatti, Federica Sallusto, Robin Weiss, Antonio Lanzavecchia, and Winfried Weissenhorn. Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41. PLoS Pathog., 6(11):e1001195, 2010. PubMed ID: 21124990. Show all entries for this paper.

Sattentau1995b Q. J. Sattentau. Conservation of HIV-1 gp120 Neutralizing Epitopes after Formalin Inactivation. AIDS, 9:1383-1385, 1995. PubMed ID: 8605064. Show all entries for this paper.

Sattentau1996 Q. J. Sattentau. Neutralization of HIV-1 by Antibody. Curr. Opin. Immunol., 8:540-545, 1996. Review. PubMed ID: 8794008. Show all entries for this paper.

Scheid2009 Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Michael S. Seaman, Klara Velinzon, John Pietzsch, Rene G. Ott, Robert M. Anthony, Henry Zebroski, Arlene Hurley, Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373. Show all entries for this paper.

Seaman2010 Michael S. Seaman, Holly Janes, Natalie Hawkins, Lauren E. Grandpre, Colleen Devoy, Ayush Giri, Rory T. Coffey, Linda Harris, Blake Wood, Marcus G. Daniels, Tanmoy Bhattacharya, Alan Lapedes, Victoria R Polonis, Francine E. McCutchan, Peter B. Gilbert, Steve G. Self, Bette T. Korber, David C. Montefiori, and John R. Mascola. Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies. J Virol, 84(3):1439-1452, Feb 2010. PubMed ID: 19939925. Show all entries for this paper.

Sharon2002 Michal Sharon, Matthias Görlach, Rina Levy, Yehezkiel Hayek, and Jacob Anglister. Expression, Purification, and Isotope Labeling of a gp120 V3 Peptide and Production of a Fab from a HIV-1 Neutralizing Antibody for NMR Studies. Protein Expr. Purif., 24(3):374-383, Apr 2002. PubMed ID: 11922753. Show all entries for this paper.

Sharpe2004 Simon Sharpe, Naama Kessler, Jacob A. Anglister, Wai-Ming Yau, and Robert Tycko. Solid-State NMR Yields Structural Constraints on the V3 Loop from HIV-1 Gp120 Bound to the 447-52D Antibody Fv Fragment. J. Am. Chem. Soc., 126(15):4979-4990, 21 Apr 2004. PubMed ID: 15080704. Show all entries for this paper.

Shen2010 Xiaoying Shen, S. Moses Dennison, Pinghuang Liu, Feng Gao, Frederick Jaeger, David C. Montefiori, Laurent Verkoczy, Barton F. Haynes, S. Munir Alam, and Georgia D. Tomaras. Prolonged Exposure of the HIV-1 gp41 Membrane Proximal Region with L669S Substitution. Proc. Natl. Acad. Sci. U.S.A., 107(13):5972-5977, 30 Mar 2010. PubMed ID: 20231447. Show all entries for this paper.

Shibata2007 Junji Shibata, Kazuhisa Yoshimura, Akiko Honda, Atsushi Koito, Toshio Murakami, and Shuzo Matsushita. Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate. J. Virol., 81(8):3757-3768, Apr 2007. PubMed ID: 17251298. Show all entries for this paper.

Shmelkov2011 Evgeny Shmelkov, Arthur Nadas, James Swetnam, Susan Zolla-Pazner, and Timothy Cardozo. Indirect Detection of an Epitope-Specific Response to HIV-1 gp120 Immunization in Human Subjects. PLoS One, 6(11):e27279, 2011. PubMed ID: 22076145. Show all entries for this paper.

Shmelkov2014 Evgeny Shmelkov, Chavdar Krachmarov, Arsen V. Grigoryan, Abraham Pinter, Alexander Statnikov, and Timothy Cardozo. Computational Prediction of Neutralization Epitopes Targeted by Human Anti-V3 HIV Monoclonal Antibodies. PLoS One, 9(2):e89987, 2014. PubMed ID: 24587168. Show all entries for this paper.

Smalls-Mantey2012 Adjoa Smalls-Mantey, Nicole Doria-Rose, Rachel Klein, Andy Patamawenu, Stephen A. Migueles, Sung-Youl Ko, Claire W. Hallahan, Hing Wong, Bai Liu, Lijing You, Johannes Scheid, John C. Kappes, Christina Ochsenbauer, Gary J. Nabel, John R. Mascola, and Mark Connors. Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding. J. Virol., 86(16):8672-8680, Aug 2012. PubMed ID: 22674985. Show all entries for this paper.

Smith1998 A. D. Smith, S. C. Geisler, A. A. Chen, D. A. Resnick, B. M. Roy, P. J. Lewi, E. Arnold, and G. F. Arnold. Human Rhinovirus Type 14: Human Immunodeficiency Virus Type 1 (HIV-1) V3 Loop Chimeras from a Combinatorial Library Induce Potent Neutralizing Antibody Responses against HIV-1. J. Virol., 72:651-659, 1998. The tip of the MN V3 loop, IGPGRAFYTTKN, was inserted into cold-causing human rhinovirus 14 (HRV14) and chimeras were immunoselected using MAbs 447-52-D, 694/98-D, NM-01, and 59.1, for good presentation of the V3 antigenic region. The selected chimeric viruses were neutralized by anti-V3 loop MAbs. The chimeric viruses elicited potent NAbs against ALA-1 and MN in guinea pigs. PubMed ID: 9420270. Show all entries for this paper.

Spear1993 G. T. Spear, D. M. Takefman, B. L. Sullivan, A. L. Landay, and S. Zolla-Pazner. Complement activation by human monoclonal antibodies to human immunodeficiency virus. J. Virol., 67:53-59, 1993. This study looked at the ability of 16 human MAbs to activate complement. MAbs directed against the V3 region could induce C3 deposition on infected cells and virolysis of free virus, but antibodies to the CD4BS and C-terminal region and two regions in gp41 could induce no complement mediated effects. Pre-treatment with sCD4 could increase complement-mediated effects of anti-gp41 MAbs, but decreased the complement-mediated effects of V3 MAbs. Anti-gp41 MAbs were able to affect IIIB but not MN virolysis, suggesting spontaneous shedding of gp120 on IIIB virions exposes gp41 epitopes. IgG isotype did not appear to have an effect on virolysis or C3 deposition. PubMed ID: 7677959. Show all entries for this paper.

Sreepian2009 Apichai Sreepian, Jongruk Permmongkol, Wannee Kantakamalakul, Sontana Siritantikorn, Nattaya Tanlieng, and Ruengpung Sutthent. HIV-1 Neutralization by Monoclonal Antibody against Conserved Region 2 and Patterns of Epitope Exposure on the Surface of Native Viruses. J. Immune Based Ther. Vaccines, 7:5, 2009. PubMed ID: 19821992. Show all entries for this paper.

Srivastava2002 Indresh K. Srivastava, Leonidas Stamatatos, Harold Legg, Elaine Kan, Anne Fong, Stephen R. Coates, Louisa Leung, Mark Wininger, John J. Donnelly, Jeffrey B. Ulmer, and Susan W. Barnett. Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol., 76(6):2835-2847, Mar 2002. URL: http://jvi.asm.org/cgi/content/full/76/6/2835. PubMed ID: 11861851. Show all entries for this paper.

Srivastava2008 Indresh K. Srivastava, Elaine Kan, Yide Sun, Victoria A. Sharma, Jimna Cisto, Brian Burke, Ying Lian, Susan Hilt, Zohar Biron, Karin Hartog, Leonidas Stamatatos, Ruben Diaz-Avalos, R Holland Cheng, Jeffrey B. Ulmer, and Susan W. Barnett. Comparative Evaluation of Trimeric Envelope Glycoproteins Derived from Subtype C and B HIV-1 R5 Isolates. Virology, 372(2):273-290, 15 Mar 2008. PubMed ID: 18061231. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

Stanfield2006 Robyn L. Stanfield, Miroslaw K. Gorny, Susan Zolla-Pazner, and Ian A. Wilson. Crystal Structures of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralizing Antibody 2219 in Complex with Three Different V3 Peptides Reveal a New Binding Mode for HIV-1 Cross-Reactivity. J. Virol., 80(12):6093-6105, Jun 2006. PubMed ID: 16731948. Show all entries for this paper.

Swetnam2010 James Swetnam, Evgeny Shmelkov, Susan Zolla-Pazner, and Timothy Cardozo. Comparative Magnitude of Cross-Strain Conservation of HIV Variable Loop Neutralization Epitopes. PLoS One, 5(12):e15994, 2010. PubMed ID: 21209919. Show all entries for this paper.

Tasca2008 Silvana Tasca, Siu-Hong Ho, and Cecilia Cheng-Mayer. R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch. J. Virol., 82(14):7089-7099, Jul 2008. PubMed ID: 18480460. Show all entries for this paper.

Teeraputon2005 Sirilak Teeraputon, Suda Louisirirojchanakul, and Prasert Auewarakul. N-Linked Glycosylation in C2 Region of HIV-1 Envelope Reduces Sensitivity to Neutralizing Antibodies. Viral Immunol., 18(2):343-353, Summer 2005. PubMed ID: 16035946. Show all entries for this paper.

Tomaras2011 Georgia D. Tomaras, James M. Binley, Elin S. Gray, Emma T. Crooks, Keiko Osawa, Penny L. Moore, Nancy Tumba, Tommy Tong, Xiaoying Shen, Nicole L. Yates, Julie Decker, Constantinos Kurt Wibmer, Feng Gao, S. Munir Alam, Philippa Easterbrook, Salim Abdool Karim, Gift Kamanga, John A. Crump, Myron Cohen, George M. Shaw, John R. Mascola, Barton F. Haynes, David C. Montefiori, and Lynn Morris. Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals. J. Virol., 85(21):11502-11519, Nov 2011. PubMed ID: 21849452. Show all entries for this paper.

Totrov2010 Maxim Totrov, Xunqing Jiang, Xiang-Peng Kong, Sandra Cohen, Chavdar Krachmarov, Aidy Salomon, Constance Williams, Michael S. Seaman, Ruben Abagyan, Timothy Cardozo, Miroslaw K. Gorny, Shixia Wang, Shan Lu, Abraham Pinter, and Susan Zolla-Pazner. Structure-Guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold. Virology, 405(2):513-523, 30 Sep 2010. PubMed ID: 20663531. Show all entries for this paper.

Upadhyay2014 Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106. Show all entries for this paper.

Vaine2010 Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David Montefiori, Paul Goepfert, M. Juliana McElrath, and Shan Lu. Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies. PLoS One, 5(11):e13916, 2010. PubMed ID: 21085486. Show all entries for this paper.

vanGils2011 Marit J. van Gils, Evelien M. Bunnik, Brigitte D. Boeser-Nunnink, Judith A. Burger, Marijke Terlouw-Klein, Naomi Verwer, and Hanneke Schuitemaker. Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies. J. Virol., 85(14):6986-6995, Jul 2011. PubMed ID: 21593147. Show all entries for this paper.

Varadarajan2005 Raghavan Varadarajan, Deepak Sharma, Kausik Chakraborty, Mayuri Patel, Michael Citron, Prem Sinha, Ramkishor Yadav, Umar Rashid, Sarah Kennedy, Debra Eckert, Romas Geleziunas, David Bramhill, William Schleif, Xiaoping Liang, and John Shiver. Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design. J. Virol., 79(3):1713-1723, Feb 2005. PubMed ID: 15650196. Show all entries for this paper.

Vermeire2009 Kurt Vermeire, Kristel Van Laethem, Wouter Janssens, Thomas W. Bell, and Dominique Schols. Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol., 83(18):9577-9583, Sep 2009. PubMed ID: 19570853. Show all entries for this paper.

Verrier2001 F. Verrier, A. Nadas, M. K. Gorny, and S. Zolla-Pazner. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J. Virol., 75(19):9177--86, Oct 2001. URL: http://jvi.asm.org/cgi/content/full/75/19/9177. PubMed ID: 11533181. Show all entries for this paper.

Visciano2008 Maria Luisa Visciano, Michael Tuen, Miroslaw K. Gorny, and Catarina E. Hioe. In Vivo Alteration of Humoral Responses to HIV-1 Envelope Glycoprotein gp120 by Antibodies to the CD4-Binding Site of gp120. Virology, 372(2):409-420, 15 Mar 2008. PubMed ID: 18054978. Show all entries for this paper.

Wang2007a Bao-Zhong Wang, Weimin Liu, Sang-Moo Kang, Munir Alam, Chunzi Huang, Ling Ye, Yuliang Sun, Yingying Li, Denise L. Kothe, Peter Pushko, Terje Dokland, Barton F. Haynes, Gale Smith, Beatrice H. Hahn, and Richard W. Compans. Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles. J. Virol., 81(20):10869-10878, Oct 2007. PubMed ID: 17670815. Show all entries for this paper.

Wu2008 Xueling Wu, Anna Sambor, Martha C. Nason, Zhi-Yong Yang, Lan Wu, Susan Zolla-Pazner, Gary J. Nabel, and John R. Mascola. Soluble CD4 Broadens Neutralization of V3-Directed Monoclonal Antibodies and Guinea Pig Vaccine Sera against HIV-1 Subtype B and C Reference Viruses. Virology, 380(2):285-295, 25 Oct 2008. PubMed ID: 18804254. Show all entries for this paper.

Wu2010 Xueling Wu, Zhi-Yong Yang, Yuxing Li, Carl-Magnus Hogerkorp, William R. Schief, Michael S. Seaman, Tongqing Zhou, Stephen D. Schmidt, Lan Wu, Ling Xu, Nancy S. Longo, Krisha McKee, Sijy O'Dell, Mark K. Louder, Diane L. Wycuff, Yu Feng, Martha Nason, Nicole Doria-Rose, Mark Connors, Peter D. Kwong, Mario Roederer, Richard T. Wyatt, Gary J. Nabel, and John R. Mascola. Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1. Science, 329(5993):856-861, 13 Aug 2010. PubMed ID: 20616233. Show all entries for this paper.

Xu2010 Hengyu Xu, Likai Song, Mikyung Kim, Margaret A. Holmes, Zane Kraft, George Sellhorn, Ellis L. Reinherz, Leonidas Stamatatos, and Roland K. Strong. Interactions between Lipids and Human Anti-HIV Antibody 4E10 Can Be Reduced without Ablating Neutralizing Activity. J. Virol., 84(2):1076-1088, Jan 2010. PubMed ID: 19906921. Show all entries for this paper.

Yamamoto2008 Hiroyuki Yamamoto and Tetsuro Matano. Anti-HIV Adaptive Immunity: Determinants for Viral Persistence. Rev. Med. Virol., 18(5):293-303, Sep-Oct 2008. PubMed ID: 18416450. Show all entries for this paper.

Yang2010a Qiang Yang, Cishan Li, Yadong Wei, Wei Huang, and Lai-Xi Wang. Expression, Glycoform Characterization, and Antibody-Binding of HIV-1 V3 Glycopeptide Domain Fused with Human IgG1-Fc. Bioconjug. Chem., 21(5):875-883, 19 May 2010. PubMed ID: 20369886. Show all entries for this paper.

Yates2018 Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288. Show all entries for this paper.

Yoshimura2006 Kazuhisa Yoshimura, Junji Shibata, Tetsuya Kimura, Akiko Honda, Yosuke Maeda, Atsushi Koito, Toshio Murakami, Hiroaki Mitsuya, and Shuzo Matsushita. Resistance Profile of a Neutralizing Anti-HIV Monoclonal Antibody, KD-247, that Shows Favourable Synergism with Anti-CCR5 Inhibitors. AIDS, 20(16):2065-2073, 24 Oct 2006. PubMed ID: 17053352. Show all entries for this paper.

Yu2010 Bin Yu, Dora P. A. J. Fonseca, Sara M. O'Rourke, and Phillip W. Berman. Protease Cleavage Sites in HIV-1 gp120 Recognized by Antigen Processing Enzymes Are Conserved and Located at Receptor Binding Sites. J. Virol., 84(3):1513-1526, Feb 2010. PubMed ID: 19939935. Show all entries for this paper.

Yu2018 Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, and Galit Alter. Exploiting Glycan Topography for Computational Design of Env Glycoprotein Antigenicity. PLoS Comput. Biol., 14(4):e1006093, Apr 2018. PubMed ID: 29677181. Show all entries for this paper.

Yuste2006 Eloisa Yuste, Hannah B. Sanford, Jill Carmody, Jacqueline Bixby, Susan Little, Michael B. Zwick, Tom Greenough, Dennis R. Burton, Douglas D. Richman, Ronald C. Desrosiers, and Welkin E. Johnson. Simian Immunodeficiency Virus Engrafted with Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Epitopes: Replication, Neutralization, and Survey of HIV-1-Positive Plasma. J. Virol., 80(6):3030-3041, Mar 2006. PubMed ID: 16501112. Show all entries for this paper.

Zhou2010 Tongqing Zhou, Ivelin Georgiev, Xueling Wu, Zhi-Yong Yang, Kaifan Dai, Andrés Finzi, Young Do Kwon, Johannes F. Scheid, Wei Shi, Ling Xu, Yongping Yang, Jiang Zhu, Michel C. Nussenzweig, Joseph Sodroski, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, and Peter D. Kwong. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science, 329(5993):811-817, 13 Aug 2010. PubMed ID: 20616231. Show all entries for this paper.

Zolla-Pazner1995 S. Zolla-Pazner, J. O'Leary, S. Burda, M. K. Gorny, M. Kim, J. Mascola, and F. McCutchan. Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry. J. Virol., 69:3807-3815, 1995. A set of 13 human MAbs to a variety of epitopes were tested against a panel of primary isolates of HIV-1, representing different genetic clades. The V3 loop tended to be B clade restricted, and a single gp120 C-terminus binding antibody was clade specific. Two other gp120 C-terminus binding antibodies were group specific. PubMed ID: 7745728. Show all entries for this paper.

Zolla-Pazner1995a S. Zolla-Pazner and S. Sharpe. A Resting Cell Assay for Improved Detection of Antibody-Mediated Neutralization of HIV Type 1 Primary Isolates. AIDS Res. Hum. Retroviruses, 11:1449-1458, 1995. PubMed ID: 8679288. Show all entries for this paper.

Zolla-Pazner1999a S. Zolla-Pazner, M. K. Gorny, P. N. Nyambi, T. C. VanCott, and A. Nadas. Immunotyping of Human Immunodeficiency Virus Type 1 (HIV): An Approach to Immunologic Classification of HIV. J. Virol., 73:4042-4051, 1999. 21 human anti-V3 MAbs were studied with respect to cross-clade reactivity and immunological relationship to other human anti-V3 MAbs. Broad cross-reactivities were observed, and V3 peptides were grouped into immunotypes that contained peptides from several clades. PubMed ID: 10196300. Show all entries for this paper.

Zolla-Pazner1999b S. Zolla-Pazner, M. K. Gorny, and P. N. Nyambi. The implications of antigenic diversity for vaccine development. Immunol. Lett., 66:159-64, 1999. PubMed ID: 10203049. Show all entries for this paper.

Displaying record number 501

Download this epitope record as JSON.

MAb ID	59.1 (R/V3-59.1)
HXB2 Location	gp160(312-317) DNA(7158..7175)	gp160 Epitope Map
Author Location	gp120(308-313 MN)
Research Contact	Mary White-Scharf and A. Profy, Repligen Corporation
Epitope	`GPGRAF`	Epitope Alignment
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	L
Species (Isotype)	mouse(IgG1)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, review, structure

Vaccine Details

Vaccine type	peptide
Vaccine strain	B clade MN
Vaccine component	Env V3

Notes

Showing 15 of 15 notes.

59.1: Data is summarized on the X-ray crystal structures resolution and NMR studies of 59.1. Sirois2007 (review, structure)
59.1: Angle of interaction between 59.1 and V3 was shown by superimposing the Fab fragment of the Ab with V3. Pantophlet2008 (antibody binding site, structure)
59.1: The crystal structure of V3-reactive antibody-peptide complexes were examined. 59.1 completely surrounded V3, suggesting a high degree of accessibility for generating an immune response. Accessibility of V3 to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
59.1: This review summarizes data on crystallographic structures of 59.1 binding to its V3 peptide antigens. Conformation of the V3 peptide bound to 59.1 is very similar to its conformation when bound to 447-52D. Stanfield2005 (antibody binding site, review, structure)
59.1: Abs against the V3 loop (50.1, 58.2, 59.1, 257-D, 268-D, 447-52D), CD4BS (IgG1b12, 559-64D, F105), CD4i (17b), and to gp41 (2F5, F240) each showed similar binding efficiency to Env derived from related pairs of primary and TCLA lines (primary: 168P and 320SI, and TCLA: 168C and 320SI-C3.3), but the TCLA lines were much more susceptible to neutralization suggesting that the change in TCLA lines that make them more susceptible to NAbs alters some step after binding. York2001
59.1: The crystal structure of V3 loop peptides bound to Fabs was obtained -- conformational changes in the tip of the V3 loop (GPGR) were observed when different MAbs were bound. Stanfield1999
59.1: The tip of the MN V3 loop was inserted into cold causing human rhinovirus 14 (HRV14) -- chimeras were immunoselected, and chimeric viruses were neutralized by anti-V3 loop antibodies, and 59.1 was among the Abs used -- chimeric viruses elicited potent NAbs in guinea pigs against ALA-1 and MN. Smith1998
59.1: A conformationally restricted analog of the tip of the V3 loop was constructed and bound with Fab 59.1 -- crystal structure shows interactions between 59.1 and an MN peptide and 59.1 and the modified peptide are similar, but NMR studies reveal that the modified peptide is more ordered in solution, retaining the Fab bound form. Ghiara1997
59.1: Competition ELISAs with serial deletions produced longer estimate of epitope length than x-ray crystallography or Alanine substitution, RIHIGPGRAFYTT, suggesting significance of non-contact residues. Seligman1996
59.1: Multi-lab study for antibody characterization and assay comparison -- neutralizes MN and IIIB. DSouza1994
59.1: Greater affinity for T-cell tropic strain T-CSF than the primary isolate JR-CSF, from which T-CSF was derived. Bou-Habib1994
59.1: Crystal structure of a 24 amino acid peptide from the V3 loop bound to 59.1 Fab fragment -- contact residues IGPGRAF. Ghiara1993
59.1: Synergistic neutralization of MN when combined with sCD4 or the CD4BS MAb F105. Potts1993
59.1: Epitope defined by peptide reactivity and binding affinity with amino acid substitutions -- GPGRAF. WhiteScharf1993 (antibody binding site, antibody generation)
59.1: Called R/V3-59.1 -- potent neutralizing MAb. DSouza1991

References

Showing 15 of 15 references.

DSouza1994 M. P. D'Souza, S. J. Geyer, C. V. Hanson, R. M. Hendry, G. Milman, and Collaborating Investigators. Evaluation of Monoclonal Antibodies to HIV-1 Envelope by Neutralization and Binding Assays: An International Collaboration. AIDS, 8:169-181, 1994. PubMed ID: 7519019. Show all entries for this paper.

Ghiara1997 J. B. Ghiara, D. C. Ferguson, A. C. Satterthwait, H. J. Dyson, and I. A. Wilson. Structure-Based Design of a Constrained Peptide Mimic of the HIV-1 V3 Loop Neutralization Site. J. Mol. Biol., 266:31-39, 1997. PubMed ID: 9054968. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

Displaying record number 1430

Download this epitope record as JSON.

MAb ID	F2A3
HXB2 Location	Env	Env Epitope Map
Author Location
Research Contact	James Robinson, Tulane University, New Orleans, LA, USA
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing
Species (Isotype)	human
Patient	LTNP
Immunogen
Keywords	antibody binding site, binding affinity, glycosylation, neutralization, polyclonal antibodies, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity

Notes

Showing 9 of 9 notes.

F2A3: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson
F2A3: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs".F2A3 was used in the anti-gp120 cocktail in the western blot experiment to prove that enzymes removed junk Env from VLPs and inactivated virus.. Crooks2011 (glycosylation)
F2A3: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. F2A3 was used as a control mAb in the comprehensive set of assays performed. Tomaras2011 (neutralization, polyclonal antibodies)
F2A3: The antigenic structure of Gag-Env pseudovirions was characterized and it was shown that these particles can recapitulate native HIV virion epitope structures. F2A2 hybridoma cell line was shown to specifically recognize the Gag-Env pseudovirions. The Gag-Env pseudovirions were further used to identify a subset of antigen-specific B cells in chronically infected HIV subjects. Hicar2010 (binding affinity, structure)
F2A3: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. Using an ELISA assay, it was shown that the V3 epitope for F2A3 Ab was lost on the CC101.19 compared to the parental virus gp120. Berro2009
F2A3: F2A3 neutralized two of the 15 subtype B isolates tested, 93TH305 and 92BR020c. Binding affinity of MAb F2A3 to gp120 was strongly reduced upon substitutions of His308, or K305 to Ala, suggesting that the F2A3 epitope overlaps mostly with the N-terminal flank of the V3 region. Binding of F2A3 was substantially enhanced by substitutions I309A, F317A, Y318A, and D325A, indicating that their interaction with neighboring residues likely affects how well F2A3 epitope is presented. F2A3 inability to neutralize 5 of the 15 viruses tested could not be explained by substitution of important contact residues. The fine specificity of F2A3 was mapped onto V3 in the structural context of gp120. This showed that the residues important for F2A3 binding form a nearly linear arrangement on the V3 structure, and that the residues that increased Ab binding when changed to Ala are crowded around the linear arrangement, suggesting an important role of the adjacent residues for contact residue positioning. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
F2A3: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. F2A3 was shown to bind specifically only to CON6 and subtype A gp140CFIs. No specific binding was observed for the CON-S nor for the rest of the recombinant proteins and the two subtype B gp120 proteins. Liao2006 (antibody binding site, vaccine antigen design, subtype comparisons)
F2A3: Yeast display was compared to phage display and shown to select all the scFv identified by phage display and additional novel antibodies. F2A3 was used in competition assays to determine the binding region of the MAbs selected from the yeast displayed antibody library. Bowley2007
F2A3: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. F2A3 has no indication of polyspecific autoreactivity. Haynes2005 (antibody binding site)

References

Showing 9 of 9 references.

Bowley2007 D. R. Bowley, A. F. Labrijn, M. B. Zwick, and D. R. Burton. Antigen Selection from an HIV-1 Immune Antibody Library Displayed on Yeast Yields Many Novel Antibodies Compared to Selection from the Same Library Displayed on Phage. Protein Eng. Des. Sel., 20(2):81-90, Feb 2007. PubMed ID: 17242026. Show all entries for this paper.

Crooks2011 Ema T. Crooks, Tommy Tong, Keiko Osawa, and James M. Binley. Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected. J. Virol., 85(12):5825-5839, Jun 2011. PubMed ID: 21471242. Show all entries for this paper.

Hicar2010 Mark D. Hicar, Xuemin Chen, Bryan Briney, Jason Hammonds, Jaang-Jiun Wang, Spyros Kalams, Paul W. Spearman, and James E. Crowe, Jr. Pseudovirion Particles Bearing Native HIV Envelope Trimers Facilitate a Novel Method for Generating Human Neutralizing Monoclonal Antibodies Against HIV. J. Acquir. Immune Defic. Syndr., 54(3):223-235, Jul 2010. PubMed ID: 20531016. Show all entries for this paper.

Tong2012 Tommy Tong, Ema T. Crooks, Keiko Osawa, and James M. Binley. HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes. J. Virol., 86(7):3574-3587, Apr 2012. PubMed ID: 22301141. Show all entries for this paper.

Displaying record number 1431

Download this epitope record as JSON.

MAb ID	LA21
HXB2 Location	Env	Env Epitope Map
Author Location
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing
Species (Isotype)	human
Patient	AC-05
Immunogen
Keywords	antibody binding site, binding affinity, glycosylation, neutralization, structure, variant cross-reactivity

Notes

Showing 5 of 5 notes.

LA21: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". LA21 was used in the anti-gp120 cocktail in the western blot experiment to prove that enzymes removed junk Env from VLPs and inactivated virus.. Crooks2011 (glycosylation)
LA21: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding of LA21 to WT VLPs is consistent with the recognition of nonfunctional Env. LA21 did not neutralize trimer VLPs. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence compared to WT VLPs. Tong2012 (neutralization, binding affinity)
LA21: LA21 neutralized two of the 15 subtype B isolates tested. Binding affinity of MAb LA21 to gp120 was strongly reduced upon substitutions of His308, or Pro313 (250-fold), to Ala. The dependence on Pro313 suggests that a precise conformation of the V3 β hairpin turn may be critical for binding of LA21. Thus, LA21 may need to interact with V3 from an angle, which does not permit access to V3 on many different primary viruses. LA21 inability to neutralize 6 of the 15 viruses tested could not be explained by substitution of important contact residues. The fine specificity of LA21 was mapped onto V3 in the structural context of gp120. This showed that the residues important for LA21 binding form a somewhat disjointed pattern, and that LA21 likely also contacts neighboring residues. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
LA21: This Ab was shown not to react with clade C gp140 (97CN54). Sheppard2007a (variant cross-reactivity)
LA21: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. LA21 has no indication of polyspecific autoreactivity. Haynes2005 (antibody binding site)

References

Showing 5 of 5 references.

Displaying record number 1647

Download this epitope record as JSON.

MAb ID	LE311
HXB2 Location	Env	Env Epitope Map
Author Location	gp120 (V3)
Research Contact	James Robinson, Tulane University, New Orleans, LA, USA
Epitope
Ab Type
Neutralizing
Species (Isotype)
Patient	AC-033
Immunogen
Keywords	antibody binding site, antibody generation, assay or method development, binding affinity, neutralization, structure, vaccine antigen design, variant cross-reactivity

Notes

Showing 5 of 5 notes.

LE311: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits competed for binding to LE311, indicating elicitation of LE311-like Abs by both immunization regimens. Competitive virus capture assay revealed higher titers of LE311-like Abs in animals immunized with DNA prime-protein boost than in protein-only immunized animals. Vaine2008 (vaccine antigen design)
LE311: LE311 neutralized three of the 15 subtype B isolates tested. Binding affinity of MAb LE311 to gp120 was strongly reduced upon substitutions of His308, Pro313, or K305 to Ala, suggesting that the LE311 epitope overlaps mostly with the N-terminal flank of the V3 region and that a precise conformation of the V3 β hairpin turn may be critical for Ab binding. Thus, LE311 may need to interact with V3 from an angle, which does not permit access to V3 on many different primary viruses.LE311 inability to neutralize 6 of the 15 viruses tested could not be explained by substitution of important contact residues. The fine specificity of LE311 was mapped onto V3 in the structural context of gp120. This showed that the residues important for LE311 binding form a nearly linear arrangement on the V3 structure. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
LE311: Guinea pigs were immunized with gp120 protein, or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env. LE311 was used in a capture assay showing that most of the SOS-VLP and UNC-VLP sera contained high titers of anti-V3 Abs. gp120 sera showed only moderate titers of V3 competing Abs. Crooks2007 (neutralization)
LE311: LE311 was investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. LE311 dramatically neutralized in the post-CD4 format but did not have any activity in the standard format. LE311 did not have any activity in the post-CD4/CCR5 format. This suggests that the post-CD4, pre-CCR5 phase of infection is a narrow window of opportunity for neutralization of JR-FL by LE311 Ab. Addition of a disulfide bridge linking gp120 and gp41 resulted in detectable activity of LE311 in the standard format. Visualization of Env-Ab binding was conducted by BN-PAGE band shifts. Crooks2005 (antibody binding site, assay or method development, neutralization)
LE311: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). LE311-like Abs were present in low titers in sera from gp140 immunized animals and in higher titers in the SHIV-infected animal. LE311 captured JRFL more efficiently when the virus was pre-incubated with sCD4. Derby2006 (antibody generation, neutralization)

References

Showing 5 of 5 references.

Isolation Paper
Derby2006 Nina R. Derby, Zane Kraft, Elaine Kan, Emma T. Crooks, Susan W. Barnett, Indresh K. Srivastava, James M. Binley, and Leonidas Stamatatos. Antibody Responses Elicited in Macaques Immunized with Human Immunodeficiency Virus Type 1 (HIV-1) SF162-Derived gp140 Envelope Immunogens: Comparison with Those Elicited during Homologous Simian/Human Immunodeficiency Virus SHIVSF162P4 and Heterologous HIV-1 Infection. J. Virol., 80(17):8745-8762, Sep 2006. PubMed ID: 16912322. Show all entries for this paper.

Crooks2007 Emma T. Crooks, Penny L. Moore, Michael Franti, Charmagne S. Cayanan, Ping Zhu, Pengfei Jiang, Robbert P. de Vries, Cheryl Wiley, Irina Zharkikh, Norbert Schülke, Kenneth H. Roux, David C. Montefiori, Dennis R. Burton, and James M. Binley. A Comparative Immunogenicity Study of HIV-1 Virus-Like Particles Bearing Various Forms of Envelope Proteins, Particles Bearing no Envelope and Soluble Monomeric gp120. Virology, 366(2):245-262, 30 Sep 2007. PubMed ID: 17580087. Show all entries for this paper.

Vaine2008 Michael Vaine, Shixia Wang, Emma T. Crooks, Pengfei Jiang, David C. Montefiori, James Binley, and Shan Lu. Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination. J. Virol., 82(15):7369-7378, Aug 2008. PubMed ID: 18495775. Show all entries for this paper.

Displaying record number 1866

Download this epitope record as JSON.

MAb ID	F530
HXB2 Location	Env	Env Epitope Map
Author Location	gp120 (V3)
Research Contact	Cavacini L
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing
Species (Isotype)	human
Patient
Immunogen	HIV-1 infection
Keywords	antibody binding site, binding affinity, neutralization, structure, variant cross-reactivity

Notes

Showing 1 of 1 note.

F530: F530 neutralized 5 of the 15 subtype B isolates tested. Binding affinity of MAb F530 to gp120 was diminished by similar substitutions as for MAbs CO11, F2A3, LA21 and LE11. However, the binding affinity of F530 was not diminished by the His308 to Ala change. F530 inability to neutralize 6 of the 15 viruses tested could not be explained by substitution of important contact residues. The fine specificity of F530 was mapped onto V3 in the structural context of gp120. The map was similar to the maps of MAbs CO11, F2A3, LA21 and LE311, however, the ability of F530 to bind V3 without requiring the presence of Arg315 suggests that F350 interacts mostly with the N-terminal flank of the V3 loop. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)

References

Showing 1 of 1 reference.

Displaying record number 1089

Download this epitope record as JSON.

MAb ID	2219
HXB2 Location	Env	Env Epitope Map
Author Location	(gp120 JRCSF)
Research Contact	Susan Zolla-Pazner (Zollas01@mcrcr6.med.nyu) (NYU Med. Center)
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P View neutralization details
Species (Isotype)	human(IgG1λ)
Patient
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody lineage, antibody sequence, assay or method development, binding affinity, broad neutralizer, computational epitope prediction, glycosylation, mimotopes, neutralization, optimal epitope, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 31 of 31 notes.

2219: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q). Yates2018 (vaccine antigen design, vaccine-induced immune responses, binding affinity)
2219: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. deTaeye2018 (broad neutralizer)
2219: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. The V3 MAbs tested were: 447, 2219, and 2557. Upadhyay2014 (glycosylation, neutralization)
2219: A computational method, MDE, predicts the presence of neutralization epitopes in the V3 loop solely from the viral sequence and the crystal structure of the antibody. For V3-specific mAbs 2219 and 447-52D, the method accurately predicted the presence of neutralization epitopes in diverse strains of HIV-1. Identification of Ab-targeted neutralization epitopes in silico enables easy prediction of the reactivity of specific mAbs across diverse variants, and facilitates rational design of immunogens. Shmelkov2014 (computational epitope prediction)
2219: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. 2219 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab. Klein2013 (neutralization, structure, antibody lineage)
2219: Signature motifs specific for neutralization epitopes present in the V3 loop crown were used to determine the presence or absence of MAb-specific epitopes in vaccine immunogens and in break-through viruses infecting vaccine and placebo recipients in the VAX003 and VAX004 Phase III clinical trials. Of the six epitopes present in the immunogens and targeted by known NAbs, only the one targeted by anti-V3 NAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects from VAX003 Thailand cohort compared to the placebo group. It is suggested that a specific 2219-like human neutralizing antibody immune response to AIDSVAX immunization occurred in the VAX003 cohort, and that this response protected subjects from a narrow subset of HIV-1 viruses circulating in Thailand in the 1990s. The signature motif used for MAb 2219 is R9, K10, [I,V]12, [Y,F]21 in V3-loop position numbers. Shmelkov2011 (vaccine-induced immune responses)
2219: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates. Haldar2011 (neutralization)
2219: VH5-51 gene segment was used by 18 of 51 (35%) anti-V3 MAbs. This study analyzed the crystal structure of 5 Fabs encoded by VH5-51/VL lambda genes. Each Fab interacted with key residues at the same 7 positions in the crown of the V3 loop, although the amino acids could vary, suggesting that while V3 is variable in sequence and structurally flexible, a common structure is retained across strains. MAb 2219 interacted with amino acids R304, K305, I307, H308, I309, F317, Y318 of MN V3 peptide. Most of MAb 2219 contact residues were also present at the corresponding positions of the germline VH5-51 gene. All 18 VH5-51 using MAbs were studied with a constrained peptide mimotope which preserved the 3D of the VH5-51 derived MAbs 2219,2557, 1006, but did not react with other anti-V3 MAbs that recognize different V3 epitopes. 14/18 (2219 included) were reactive with the mimotope, compared to only 1/30 non-VH5-51 MAbs. Gorny2011 (mimotopes, antibody sequence, structure)
2219: Masking signatures were developed and analyzed for 4 anti-HIV V3 loop MAbs, 2219, 3074, 2557, 447-52D. The epitopes were classified as "masked" if their signature motifs were present in a virus, but there was no detectible neutralization by the MAb of the same virus in vitro. The signature motif for MAb 2219 used in the study was R9+K10+[l,V]12+[Y,F]21. Of the 4 MAbs, 2219 neutralized the largest number of pseudoviruses containing its epitope. The 2219 neutralization epitope is unmasked in 25/68 (36.8%) of the viruses containing the 2219 epitope. Agarwal2011 (neutralization)
2219: Structure of 2219 bound to a peptide containing the sequence of the V3 loop was used to derive sensitive and specific signature motifs for its neutralization epitope. 2219 epitope (⁹RKx[I,V]xxxxxxxx[Y,F]²¹) was found conserved in 56% of circulating HIV-1 strains from all major subtypes. 2219 neutralized 18% of subtype A pseudovirions, 49% of subtype B, 29% of subtype C, 10% of subtype D and 0% of CRF02_AG. Swetnam2010 (antibody binding site, neutralization, variant cross-reactivity, subtype comparisons, structure)
2219: 2219 neutralizing activity was assessed against pseudoviruses expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infection. IC50 neutralization activity was also statistically assessed based on the area under the neutralization curves (AUC). 2219 was able to neutralize 15/57 viruses in U87-based assay and 10/41 viruses in TZM-based assay, including Tier 1 and Tier 2 viruses, viruses of subtypes B, C, D, and viruses from both chronic and acute infections. AUC analysis revealed that 24/57 viruses in the U87-based assay, and 11/41 viruses in the TZM-based assay, were significantly neutralized by this Ab. Thus, the AUC method has the ability to detect low levels of neutralizing activity that otherwise may be missed. Hioe2010 (assay or method development, neutralization, variant cross-reactivity)
2219: Two V3-scaffold immunogen constructs were designed and expressed using 3D structures of cholera toxin B (CTB), V3 in the gp120 context, and V3 bound to 447-52D MAb. The construct (V3-CTB) presenting the complete V3 was recognized by 2219 MAb and by the large majority of other MAbs (18/24), indicating correctly folded and exposed MAb epitopes. V3-CTB induced V3-binding Abs and Abs displaying cross-clade neutralizing activity in immunized rabbits. Short V3-CTB construct, presenting a V3 fragment in conformation observed in complex with 447-52D, was recognized by 2219, but only at the highest MAb concentrations. Totrov2010 (vaccine antigen design, binding affinity, structure)
2219: Crystal structures of 2219 Fab in complex with different V3 peptides revealed that 2219 interactions with V3 are highly similar to those of MAbs 2557 and 1006-15D. Like 2557, 2219 interactions with V3 can be divided into three regions: the arch, the circlet, and the band, with the arch and the band specific residues identical between these two MAbs. The results indicate that 2219, 2557 and 1006-15D recognize V3 using similar modes of binding. It is shown that broadly-reactive Abs can bind to conserved elements in four regions of the V3: the arch, the circlet, the band, and the V3 peptide main chain backbone. These conserved elements are either unaffected by or are subjected to minimal sequence variation. A mimotope that preserved the key structural elements in the circlet and band regions, but with GPG of the arch replaced by a disulfide bond, interacted with broadly reactive MAbs 2557, 1006 and 2219. It did not react with 447-52D nor 268-D, which are dependent on the Arg in the arch. Thus, mimotopes can be constructed that may focus the immune response on structurally conserved elements. Jiang2010 (antibody binding site, mimotopes, structure)
2219: Ab specificities of a panel of HIV sera were systematically analyzed by selective adsorption with native gp120 and specific mutant variants. To test sera for presence of V3 neutralizing activity, V3 peptides were used. These peptides inhibited neutralization mediated by 2219. Sera with limited neutralizing activity were mapped to V3. In some of the broadly neutralizing sera, the gp120-directed neutralization was mapped to CD4bs. Some sera were positive for NAbs against coreceptor binding region. A subset of sera also contained NAbs directed against MPER. Li2009c (assay or method development)
2219: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for 2219 were smaller than those for VRC01. Zhou2010 (neutralization, structure)
2219: The epitope sequence motif of 2219 was precisely defined based on the 3D structure of the MAb complexed with V3MN peptide. The specific epitope motif suggested by the complex structure was shown to be K307, I309 and Y318. A set of V3 chimeric pseudoviruses, carrying or not carrying the determined 2219 sequence motif, were tested for their sensitivity to neutralization by 2219. Viruses carrying the 2219 epitope sequence motif were neutralized very well by 2219 while viruses lacking this motif were not neutralized at all. The neutralization-relevant epitope sequence motif of 2219 was calculated to be present in approximately 30% of worldwide HIV isolates, and equally distributed among subtypes. Cardozo2009 (neutralization, optimal epitope)
2219: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:5-51*03, IGHD:4-17, D-RF:2, IGHJ:3. There was a preferential usage of the VH5-51 gene segment for V3 Abs. The usage of the VH4 family for the V3 Abs was restricted to only one gene segment, VH4-59, and the VH3 gene family was used at a significantly lower level by these Abs. The V3 Abs preferentially used the JH3 and D2-15 gene segments. Gorny2009 (antibody sequence)
2219: Data is summarized on the X-ray crystal structures resolution and NMR studies of 2219. Sirois2007 (review, structure)
2219: 2219 structure, binding, neutralization, and strategies that can be used for vaccine antigen design to elicit anti-V3 Abs, are reviewed in detail. Lin2007 (review)
2219: To test whether the conformation change of Env induced by CD4 affects the breadth and potency of 2219 neutralization, 2219 was tested in the presence or absence of sCD4 in neutralization of a panel of 12 subtype B and 12 subtype C Env-pseudoviruses. Without sCD4, 2219 neutralized 2 subtype B and 0 subtype C viruses. With sCD4 present, 2219 neutralized 9 subtype B and 1 subtype C virus, indicating that neutralization resistance of some viruses to 2219 is due to a lack of exposure of the V3 loop. Neutralization of JRFL, ADA, and YU2 isolates by 2219 increased with increased dose of sCD4. Wu2008 (neutralization, variant cross-reactivity)
2219: Angle of interaction between 2219 and V3 was shown by superimposing the Fab fragment of the Ab with V3. Pantophlet2008 (antibody binding site, structure)
2219: This Ab was shown to neutralize SF162 and the neutralization sensitivity increased somewhat in the SF162 variant with a JR-FL V3 loop, SF162(JR-FL V3). In contrast, a great reduction in sensitivity to neutralization was observed in the SF162(JR-FL V1/V2) variant and was somewhat restored in the SF162(JR-FL V1/V2/V3) variant, indicating that the masking of the V1/V2 loop plays a much greater role in restricting neutralization sensitivity than the variations in V3. This Ab was shown to neutralize viruses with V3 sequences from several different subtypes (B, F, A1, C, CRF02_AG, CRF01_AE and H). This Ab failed to neutralize SF162(JR-FL V1/V2) with V3 derived from different HIV-1 clades indicating effective V1/V2-mediated masking of several HIV-1 clades. The effect on the neutralization sensitivity of the residue at the crown of the V3 loop (position 18) was shown to be low for this Ab. Krachmarov2006 (neutralization, variant cross-reactivity, subtype comparisons)
2219: Structure of 2219 Ab in contact with three different V3 peptides was determined in order to gain insight in the structural basis for its cross-reactivity with different HIV-1 clades. It is shown that Fab 2219 binds to one face of the variable V3 beta-hairpin, primarily contacting conserved residues, leaving the V3 crown largely accessible. Twisting of the V3 loop is shown to alter the relative dispositions and pairing of amino acids. 2219 was shown to cross-react with V3 sequences from clades A, B and C and to neutralize viruses from clades A, B and F. Stanfield2006 (antibody binding site, variant cross-reactivity, subtype comparisons, structure)
2219: This MAb was derived from plasma from a patient with env clade B virus with the GPGR V3 motif. When cross-reactivity was tested, this Ab bound to the V3subtypeB-fusion protein containing GPGR motif and to V3subtypeA-fusion protein containing GPGQ motif. This Ab was also shown to be able to neutralize both clade B psSF162 (GPGR) and clade C psMW965 (GPGQ) virus and three of subtype B but only one of non-B primary isolates. Gorny2006 (neutralization, variant cross-reactivity, subtype comparisons)
2219: Full-length gp160 clones were derived from acute and early human HIV-1 infections and used as env-pseudotyped viruses in neutralization assays for their characterization as neutralization reference agents. 4 out of 19 pseudoviruses were sensitive to neutralization by 2219, as was the SF162.LS strain. One additional pseudovirus was sensitive at higher Ab concentrations. Li2005a (assay or method development, neutralization)
2219: This review summarizes data on 2219-V3 and 2219-V3 peptide X-ray crystallographic structures and its neutralization capabilities. The binding mechanism of this Ab to V3 explains its ability to neutralize a wide array of HIV-1 primary isolates from different clades. Stanfield2005 (antibody binding site, neutralization, variant cross-reactivity, review, structure)
2219: This study is about the V2 MAb C108g, that is type-specific and neutralizes BaL and HXB2. JR-FL is a neutralization resistant strain; modification of JRFL at V2 positions 167 and 168 (GK->DE) created a C108g epitope, and C108g could potently neutralize the modified JR-FL. The modification in V2 also increased neutralization sensitivity to V3 MABs 4117c, 2219, 2191, and 447-52D, but only had minor effects on neutralization by CD4BS MAb 5145A, and broadly neutralizing MAbs IgG1b12, 2G12, and 2F5. Binding to CCR5 was completely inhibited by two V3 MAbs, 4117C and 2219, and was substantially inhibited by 2G12, but was not inhibited by C108g. Pinter2005 (antibody binding site)
2219: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. 5/6 anti-V3 MAbs, including 2219, had similar binding affinity to soluble SF162 and JR-FL rgp120s, although the V3 loop differs at three positions (HigpgrafyTtgE for JR-FL and TigpgrafyAtgD for SF162). Pinter2004 (variant cross-reactivity)
2219: V3 MAb neutralization is influenced by retaining the epitope, exposure on the intact virion, mobility during CD4-induced conformational change, and affinity. Anti-V3 MAbs selected using V3 peptides neutralize less effectively than V3 MAbs selected using fusion proteins or gp120, suggesting antigenic conformation is important. This MAb was selected using a JR-CSF fusion protein, and could neutralize 6/13 B clade viruses. Gorny2004 (antibody binding site)
2219: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates. The set that can cross-neutralize primary isolates (2182, 2191, 2219, 2412, 2442, 2456) bind V3 but are conformationally senstitive, suggesting some structural conservation despite sequence variation. These MAbs have distinct epitopes relative to 447-52D, a MAb directed at the tip of the V3 loop that also can neutralize many primary isolates. Inter-clade cross-neutralization by these anti-V3 MAbs is reduced. Gorny2003 (variant cross-reactivity, review, subtype comparisons)
2219: Conformation-dependent anti-V3 loop Abs may be more cross-reactive, so six new V3 MAbs were generated from cells of asymptomatic HIV-1-infected individuals by selection of heterhybridomas using a V3-fusion protein (V3-fp), the HIV-1 JRCSF V3 loop inserted into a truncated murine leukemia virus gp70 -- the six new MAbs all bind to the tip of the V3 loop and cross-compete with the MAb 447-52D and are conformationally sensitive -- MAbs showed cross-clade binding to native, intact virions of clades A(N=2), B(N=4), and F(N=2), limited binding to C(N=3) and D(N=3), and did not bind to CRF01(subtype E, N=2) -- the strength binding was highly correlated with percent neutralization using the ghost cell or PHA blast assay -- five well-characterized MAbs were used as controls: anti-V3 447-52D (anti-V3 MAb for competition and neutralization studies), 654 (anti-CD4BS used as a conformation-sensitive MAb control), 1331A (anti-C5 used as a linear binding site MAb control), MAb 246 (anti-gp41 MAb that bound to primary isolates of all clades) -- 5/6 MAbs were derived from individuals infected in the US, presumably with clade B, and one, 2182, was derived from an individual who was infected abroad with clade A who is presently living in New York city -- 2412 and 2456 were produced from cells obtained from the same individual, while the other MAbs were each generated from different subjects -- 2219 bound to 13/16 of the diverse isolates. Gorny2002 (antibody binding site, antibody generation, variant cross-reactivity, subtype comparisons)

References

Showing 31 of 31 references.

Isolation Paper
Gorny2002 Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Sandra Cohen, Victoria R. Polonis, William J. Honnen, Samuel C. Kayman, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades. J. Virol., 76(18):9035-9045, Sep 2002. PubMed ID: 12186887. Show all entries for this paper.

Gorny2011 Miroslaw K. Gorny, Jared Sampson, Huiguang Li, Xunqing Jiang, Maxim Totrov, Xiao-Hong Wang, Constance Williams, Timothy O'Neal, Barbara Volsky, Liuzhe Li, Timothy Cardozo, Phillipe Nyambi, Susan Zolla-Pazner, and Xiang-Peng Kong. Human Anti-V3 HIV-1 Monoclonal Antibodies Encoded by the VH5-51/VL Lambda Genes Define a Conserved Antigenic Structure. PLoS One, 6(12):e27780, 2011. PubMed ID: 22164215. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

Displaying record number 1121

Download this epitope record as JSON.

MAb ID	X5 (Fab X5)
HXB2 Location	Env	Env Epitope Map
Author Location	gp120(gp120 JRFL)
Epitope
Subtype	B
Ab Type	gp120 CD4i
Neutralizing	P View neutralization details
Species (Isotype)	human
Patient	FDA2
Immunogen	HIV-1 infection
Keywords	ADCC, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, antibody sequence, assay or method development, autoantibody or autoimmunity, binding affinity, chimeric antibody, co-receptor, escape, germline, glycosylation, immunotherapy, kinetics, mimics, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity

Notes

Showing 68 of 68 notes.

X5: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth. Narayan2013 (neutralization, polyclonal antibodies)
X5: The human Ab gene repertoires of uninfected and HIV-1-infected individuals were studied at genomic DNA (gDNA) and cDNA levels to determine the frequencies of putative germline Ab genes of known HIV-1 bnAbs. All libraries were deep sequenced and analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index. The human gDNA Ab libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries. This implied that the human gDNA Ab gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnmAbs. Relatively high frequencies of the VH and VKs and VLs that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. The putative germline genes were determined for a set of mAbs (b12, VRC01, VRC03, NIH45-46, 3BNC60, PG9, PGT127, and X5). Zhang2013 (antibody lineage, germline)
X5: Chimeric antigen receptors, i.e., fusion proteins made from single-chain antibodies, may be a useful approach to immunotherapy. A set of mAbs were chosen based on their binding to a variety of sites on Env and availability of antibody sequences. The chimeric receptors were created by fusing the antibody's heavy chain, light chain, and two signaling domains into a single molecule. All 7 antibodies used to make the chimeric receptors (10E8, 3BNC117, PGT126, VRC01, X5, PGT128, PG9) showed specific killing of HIV-1 infected cells and suppression of viral replication against a panel of HIV-1 strains. Ali2016 (immunotherapy, chimeric antibody)
X5: This study assessed the ADCC activity of antibodies of varied binding types, including CD4bs (b6, b12, VRC01, PGV04, 3BNC117), V2 (PG9, PG16), V3 (PGT126, PGT121, 10-1074), oligomannose (2G12), MPER (2F5, 4E10, 10E8), CD4i (17b, X5), C1/C5 (A32, C11), cluster I (240D, F240), and cluster II (98-6, 126-7). ADCC activity was correlated with binding to Env on the surfaces of virus-infected cells. ADCC was correlated with neutralization, but not always for lab-adapted viruses such as HIV-1 NLA-3. MAb X5 had moderate ADCC activity against cells infected with 1 of 3 strains tested. vonBredow2016 (ADCC)
X5: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-CD4i non-NAb X5 did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, and did not recognize or bind the immunogen either. Sanders2013 (assay or method development, neutralization, binding affinity)
X5: X-ray crystallography, surface plasmon resonance and pseudovirus neutralization were used to characterize a heavy chain only llama antibody, named JM4. The full-length IgG2b version of JM4 neutralizes over 95% of circulating HIV-1 isolates. JM4 targets a hybrid epitope on gp120 that combines elements from both the CD4 binding region and the coreceptor binding surface. JM4 epitope overlaps with the CD4i binding site of X5. Acharya2013 (antibody binding site)
X5: This study uncovered a potentially significant contribution of V_H replacement products which are highly enriched in IgH genes for the generation of anti-HIV Abs including anti-gp41, anti-V3 loop, anti-gp120, CD4i and PGT Abs. The V_H replacement "footprints" within CD4i Abs preferentially encode negatively charged amino acids within IgH CDR3. The details of X5 V_H replacement products in IgH gene and mutations and amino acid sequence analysis are described in Table 1,Table 2 and Fig 3. Liao2013a (antibody sequence)
X5: Cryoelectron tomography was used to determine structures of A12, m36, or m36/CD4 complexed to trimeric Env displayed on intact HIV-1 BaL virus. The foot print of m36 binding on gp120 is near the base of the V3 loop which resembles a "fully open" conformation similar to Ab X5. Meyerson2013 (antibody binding site, structure)
X5: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. X5 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab. Klein2013 (neutralization, structure, antibody lineage)
X5: Small sized CD4 mimetics (miniCD4s) were engineered. These miniCD4s by themselves are poorly immunogenic and do not induce anti-CD4 antibodies. Stable covalent complexes between miniCD4s and gp120 and gp140 were generated through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5 and elicited CD4i antibody responses in rabbits. A panel of MAbs of defined epitope specificities, including MAb X5, was used to analyze the antigenic integrity of the covalent complexes using capture ELISA. Martin2011 (mimics, binding affinity)
X5: X5 MAb was used to study mechanism of neutralization by bnMAbs. In contrast to VRC01, PGV04 did not enhance 17b or X5 binding to their epitopes in the co-receptor region on the gp120 monomer, and in contrast to CD4, none of the CD4bs MAbs tested induced the 17b site on trimeric cleaved Env, suggesting that a degree of mimicry of CD4 by anti-CD4bs bnMAbs may be a consequence of binding to the CD4 epitope on monomeric gp120 rather than a neutralization mechanism. Falkowska2012 (neutralization)
X5: Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies was studied by isolation of VRC01-like neutralizers with CD4bs probe; structural definition of gp120 recognition by RSC3-identified antibodies from different donors; functional complementation of heavy and light chains among VRC01-like antibodies; identification of VRC01 antibodies by 454 pyrosequencing; and cross-donor phylogenetic analysis of sequences derived from the same precursor germline gene. X5 was studied among other antibodies that derive from a common IGHV1-69 allele to assess how atypical the VRC01-like antibody convergence was. T The angular difference in heavy-chain orientation between 17b, 412d, and X5 was over 90°, or roughly 10 times as much as among the VRC01-like antibodies. X5 had 49-67% sequence identity of its heavy and light chains to respective chains of VRC-PG04 and VRC-CH31. Wu2011 (structure)
X5: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. X5 is noted in the review to be CD4i antibody and to have weak neutralizing activity against most HIV-1 isolates, with increased activity when soluble CD4 is added. Gonzalez2010 (neutralization, variant cross-reactivity, escape, review)
X5: Crystal structures of gp120 and gp41 in complex with CD4 and/or MAbs 17b, 48d, b12, b13, 412d, X5, 211C, C11, 15e, m6, m9 and F105 were used to determine the structure and the mobility of the gp41-interactive region of gp120. Elements determined to maintain the gp120-gp41 interaction were the gp120 termini and a newly described invariant 7-stranded β-sandwich. Structurally plastic elements of gp120 responsible for the various gp120 conformation changes due to receptor- or Ab-binding were structured into 3 layers, with the V1/V2 loops emanating from layer 2 and the highly glycosylated outer domain from layer 3. Pancera2010a (antibody binding site, structure)
X5: Unlike MAb m9, X5 did not compete with R5Nt for binding to gp120, indicating that the epitope for m9 differs from that of X5. Zhang2010 (antibody binding site)
X5: Molecular modeling was used to construct a 3D model of an anti-gp120 RNA aptamer, B40t77, in complex with gp120. The structure of the complex was compared to that of X5-gp120. Joubert2010 (structure)
X5: Unlike the MPER MAbs tested, X5 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions (PSV) by X5, indicating that most of the surplus Env associated with PSV was in the form of unprocessed gp160. Nontrimeric Envs from JR-CSF MC virus were also captured by X5 more efficiently than trimeric Envs from JR-FL. Leaman2010
X5: 21c binding, autoreactivity, polyreactivity and protective benefits are discussed and compared to other autoreactive MAbs, such as 2F5 and 4E10. Regulation of CD4i MAbs, such as 21c and X5, by tolerance mechanisms is discussed. Haynes2010 (autoantibody or autoimmunity, antibody polyreactivity)
X5: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. In the absence of sCD4, X5 did not bind well to the full-length trimers nor to the uncleaved ΔV1V2 trimers, but the binding was enhanced by addition of sCD4. X5 did not bind a ΔV1V2 virus carrying V120K substitution. Binding analyses of other CD4i Abs yielded slightly different results, indicating that various CD4i epitopes may be shielded to slightly different extents by the V1V2 domain. Bontjer2010 (antibody binding site, binding affinity)
X5: Neutralizing activities of X5 were similar against parent and GnTI (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps) viruses, and the N301Q mutant virus (glycan at position 301 is removed), with all viruses being resistant to neutralization by this Ab. X5 scFv complexed with sCD4 and Env trimers of parental and GnTI viruses. Binley2010 (glycosylation, neutralization)
X5: GPI-anchored and secretory scFvs of X5 were generated. GPI-scFvs were localized in the lipid raft of the plasma membrane. Cells transduced with the secretory X5 scFv showed low degree of neutralization against 3/11 tested pseudotype viruses belonging to clades A, B, B', C and E. GPI-anchored scFvs of X5 neutralized all 11 HIV-1 pseudotypes with great degree of potency. When tested against 6 wild type HIV-1 strains, secretory X5 scFv did not show any neutralization potency while X5 GPI-scFv neutralized all 6 strains with great degree of potency. sCD4 enhanced secretory X5 scFv neutralization potency but the X5 GPI-scFv neutralization was independent of sCD4 addition. In addition, GPI-scFv of X5 conferred long-term resistance to HIV-1 when expressed in human CD4+ T cells, it was shown to block HIV-1 envelope-mediated cell-cell fusion, and it blocked infection of HIV-1 captured and transferred by human DCs. Wen2010 (neutralization)
X5: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for X5 were smaller than those for VRC01. Zhou2010 (neutralization, structure)
X5: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. X5 binding and neutralization were tested for pseudoviruses with the mutations relative to the WT. X5 binding and neutralization were not affected by the these mutations. Unlike PG9 and PG16, X5 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses. Walker2010 (neutralization, binding affinity)
X5: Ab gene divergence analyses found that X5 Ab was significantly more divergent from the closest germline Abs than were hmAbs against other viruses. Germline-like X5 was constructed in a scFv format. It was shown that, unlike b12, 2G12 and 2F5, germline-like X5 bound to recombinant gp140 with high affinity. Xiao2009 (binding affinity, antibody sequence)
X5: A review about the in vivo efficacy of MAbs against HIV-1, and about inhibition of HIV-1 infection by MAb fragments (Fab, scFv), including single molecules or fusion proteins of X5. Also, the efficacy of engineered human Ab variable domains or "domain antibodies" (dAbs) as therapeutic agents is reviewed. Chen2009b (neutralization, immunotherapy, review)
X5: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:1-69*01, IGHD:3-22, D-RF:2, IGHJ:4. Non-V3 mAbs preferentially used the VH1-69 gene segment. In contrast to V3 mAbs, these non-V3 mAbs used several VH4 gene segments and the D3-9 gene segment. Similarly to the V3 mAbs, the non-V3 mAbs used the VH3 gene family in a reduced manner. Anti-CD4i mAbs exclusively used the VH1 gene family. Gorny2009 (antibody sequence)
X5: HIV-1 env sequence evolution was studied in 20 HIV-1 infected individuals undergoing treatment interruptions. By using the 3D structure of gp120 in complex with CD4 and X5, the amino acid residues that were found to be under positive selection mapped exclusively to the externally accessible residues of the gp120. There was no correlation between the number of positively selected amino acid sites and neutralizing Ab titers. Joos2007
X5: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb X5 in different HIV-1 clades is provided. McKnight2007 (variant cross-reactivity, review)
X5: This review provides information on the HIV-1 glycoprotein properties that make it challenging to target with neutralizing Abs. X5 neutralization properties and binding to HIV-1 envelope, and current strategies to develop versions of the Env spike with functional trimer properties for elicitation of broadly neutralizing Abs, are discussed. In addition, approaches to target cellular molecules, such as CD4, CCR5, CXCR4, and MHC molecules, with therapeutic Abs are reviewed. Phogat2007 (review)
X5: X5 structure, sulfation, binding, and neutralization activity are reviewed in detail. Improvement of potency and breadth of X5 neutralization is discussed. Vaccine strategies for elicitation of CD4i Abs are summarized. Lin2007 (review)
X5: This review summarizes X5 Ab epitope, properties and neutralization activity. The effect of differential CCR5 cell surface expression on X5 neutralization activity is discussed. Kramer2007 (co-receptor, neutralization, review)
X5: The various effects that neutralizing and non-neutralizing anti-envelope Abs have on HIV infection are reviewed, such as Ab-mediated complement activation and Fc-receptor mediated activities, that both can, through various mechanisms, increase and decrease the infectivity of the virus. The importance of these mechanisms in vaccine design is discussed. The unusual features of the X5 MAb are described. Willey2008 (review)
X5: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits did not compete for binding to X5, indicating no elicitation of X5-like Abs by either of the immunization regimens. Vaine2008 (vaccine antigen design)
X5: This minireview summarizes data on differences in neutralizing activities of MAbs and pooled human sera using a traditional primary cell neutralization assay and the more standardized TZM-bl reporter cell line assay. Also, suggestions are made on how to improve and standardize neutralization assays for comparable use in different laboratories. It has previously been shown that X5 neutralizes considerably better in the PBMC assay, where the CD4/CCR5 ratio is approximately 10-fold larger than in the TZM-assay cells, underscoring the role of the cell substrate in neutralization assays. In total, however, the assay discordances were shown to be bi-directional and not attributable to assay sensitivity. Polonis2008 (assay or method development, neutralization, review)
X5: Immobilized X5 was able to capture infectious HIV-1 whole virions in a standard virus capture assay, unlike mAbs 8K8 and D5. Addition of soluble CD4 enhanced significantly virion capture by X5. Nelson2008
X5: The structure of a soluble CD4-FabX5-complexed gp120 core with the V3 loop attached was used to project the results of MAb mapping onto V3 in order to obtain better understanding of the spatial organization of residues identified as important for V3 MAb binding. Pantophlet2008 (structure)
X5: A new purification method was developed using a high affinity peptide mimicking CD4 as a ligand in affinity chromatography. This allowed the separation in one step of HIV envelope monomer from cell supernatant and capture of pre-purified trimer. Binding of X5 to gp120SF162 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the miniCD4 allows the separation of HIV-1 envelope with intact X5 epitope. gp140DF162ΔV2 was purified by the miniCD4 method to assess its ability to capture gp140 trimers. Purified gp140DF162ΔV2 was recognized by X5, and the k-off value for X5 was reduced compared to gp120SF162 monomer, consistent with the gp140DF162ΔV2 trimeric conformation. Binding of X5 to gp140DF162ΔV2 purified by the miniCD4 affinity chromatography and a multi-step method was comparable, suggesting that the SF162 trimer antigenicity was preserved. Martin2008 (assay or method development, kinetics, binding affinity)
X5: Coordinates of the three-dimensional structure of trimeric Env displayed on native HIV-1 in complex with X5 were fitted on a density map, to reveal the structure of the trimeric glycoprotein spike on native HIV-1. Liu2008 (antibody binding site, structure)
X5: The study compared Ab neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. There was direct quantitative relationship between monovalent Fab-trimer binding and neutralization, implying that neutralization begins as each trimer is occupied by one Ab. In BN-PAGE, neutralizing Fabs and sCD4 were able to shift JR-FL trimers. In contrast, most non-neutralizing Fabs, bound to monomer, but their epitopes were conformationally occluded on trimers, confirming the exclusive relationship of trimer binding and neutralization. Fab X5 did not bind effectively to gp120/gp41 monomers and may therefore recognize other forms of Env. Crooks2008 (neutralization, binding affinity)
X5: Macaques were immunized with either CD4, gp120, cross-linked gp120-human CD4 complex (gp120-CD4 XL), and with single chain complex containing gp120 rhesus macaque CD4 domains 1 and 2 (rhFLSC). Sera from the rhFLSC immunized animals showed highest competition titers, being able to block gp120-CD4 complex interactions with X5 more efficiently than sera from animals immunized with the three other proteins. DeVico2007 (neutralization)
X5: Guinea pigs were immunized with gp120 protein or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env. Most of the Env-VLP sera and HIV-1+ plasma effectively blocked X5 capture. Crooks2007 (neutralization)
X5: Novel approaches based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and use of antigens with increased exposure of conserved epitopes, for enhanced identification of broadly cross-reactive neutralizing Abs are reviewed. Abs identified by these methods are described. Zhang2007 (review)
X5: The structure of the X5 MAb, particularly its CDRH3 region tyrosine sulfation, is reviewed. Also, the mechanism of its binding to the coreceptor binding site of gp120, and comparisons of the neutralizing potencies of X5 Ab fragments vs the whole IgG molecule are discussed. Engineering of Abs based on revealed structures of broadly neutralizing MAbs is discussed. Burton2005 (antibody binding site, neutralization, review, structure)
X5: The structure of the V3 region in the context of gp120 core complexed to the CD4 receptor and to the X5 Ab was determined by X-ray resolution. Comparison of free and bound X5 structure showed a large structural difference for the third complementary loop of the X5 heavy chain, representing one of the largest induced fits observed for an antibody. Accessibility of co-receptor binding site to this MAb is shown in a 3D figure. Huang2005 (antibody binding site, structure)
X5: Used as a positive control in an HIVRP assay to confirm specificity of the inhibition of viral and cellular membrane fusion by the screened scFvs. Miller2005
X5: This review summarizes data on the role of NAb in HIV-1 infection and the mechanisms of Ab protection, data on challenges and strategies to design better immunogens that may induce protective Ab responses, and data on structure and importance of MAb epitopes targeted for immune intervention. The importance of standardized assays and standardized virus panels in neutralization and vaccine studies is also discussed. Srivastava2005 (antibody binding site, neutralization, vaccine antigen design, review)
X5: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1. McCann2005 (antibody binding site, neutralization, vaccine antigen design, review)
X5: X5 was investigated in different neutralization formats, including the standard format that measures activity over the entire infection period and several formats that emphasize various stages of infection. Significant activity of X5 was induced in the post-CD4 format while it did not neutralize JR-FL in the standard format. X5 did not have any activity in the post-CD4/CCR5 format. This suggests that the post-CD4, pre-CCR5 phase of infection is a narrow window of opportunity for neutralization of JR-FL by X5 Ab. Truncation of the gp160 cytoplasmic tail or addition of a disulfide bridge linking gp120 and gp41 did not increase X5 activity. Visualization of Env-Ab binding was conducted by BN-PAGE band shifts. Crooks2005 (antibody binding site, assay or method development, neutralization)
X5: This review summarizes data on 447-52D and 2219 crystallographic structures when bound to V3 peptides and their corresponding neutralization capabilities. X5, like 447-52D and like other HIV-1 neutralizing Abs, was shown to have long CDR H3 loop, which is suggested to help Abs access recessed binding sites on the virus. Stanfield2005 (antibody binding site, review, structure)
X5: In addition to gp120-gp41 trimers, HIV-1 particles were shown to bear nonfunctional gp120-gp41 monomers and gp120-depleted gp41 stumps on their surface. X5 did not neutralize wildype virus particles and it did not bind to functional gp12-gp41 trimers. It did, however, partially react with SOS, a mutant containing a disulfide bond between gp120 and gp41. X5 is able to recognize gp120-gp41 monomers and monomeric gp120. It is hypothesized that the nonfunctional monomers on the HIV-1 surface serve to divert the Ab response, helping the virus to avoid neutralization. Moore2006 (antibody binding site, neutralization)
X5: Macaques were immunized with SF162gp140, ΔV2gp140, ΔV2ΔV3gp140 and ΔV3gp140 constructs and their antibody responses were compared to the broadly reactive NAb responses in a macaque infected with SHIV SF162P4, and with pooled sera from humans infected with heterologous HIV-1 isolates (HIVIG). X5-like Abs were elicited at low titers by ΔV3gp140 but not by the other immunogens. They were also present in the SHIV-infected macaque. Derby2006 (antibody binding site)
X5: Virus was not neutralized by X5 in a standard neutralization assay, while pre-incubation of virus with sCD4 resulted in neutralization by X5 as its epitope was exposed upon binding to CD4. Binley2006 (antibody binding site, neutralization, binding affinity)
X5: Cloned Envs (clades A, B, C, D, F1, CRF01_AE, CRF02_AG, CRF06_cpx and CRF11_cpx) derived from donors either with or without broadly cross-reactive neutralizing antibodies were shown to be of comparable susceptibility to neutralization by X5. Cham2006 (neutralization, variant cross-reactivity, subtype comparisons)
X5: Neutralization of HIV-1 primary isolates from different clades (B, C, D and E) by X5 was determined in cells expressing high or low surface concentrations of CD4 and CCR5 receptors. CD4 cell surface concentration had no effect on the inhibitory activity of this Ab while the CCR5 surface concentration had a significant effect decreasing the 50% inhibitory concentration of X5 in cell lines with low CCR5. Choudhry2006 (co-receptor, neutralization, variant cross-reactivity, subtype comparisons)
X5: A direct comparison of phage and yeast display libraries was undertaken, and yeast display sampled the immune repertoire more fully. Previous results from panning a phage library generated from a long-term non-progressor were compared directly with a yeast library. As determined by sequencing, many MAbs were common to both, although the yeast library identifies unique scFv. X5 was identified using both methods. Bowley2007 (assay or method development, binding affinity, antibody sequence)
X5: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including X5. Pantophlet2004 (vaccine antigen design)
X5: 93 viruses from different clades were tested for their neutralization cross-reactivity using a panel of HIV antibodies. X5 is a CD4i antibody and neutralized only the most sensitive B-clade envelopes in the pseudovirus assay, but was able to neutralize 2/25 non-B isolates in the PBMC assay, possibly due to differential coreceptor expression. Binley2004 (variant cross-reactivity, subtype comparisons)
X5: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three CD4i MAbs were tested; all preferentially neutralized SF162, and JRFL became neutralization sensitive to CD4i Abs if the SF162 V1V2 loop was exchanged. FAb X5 could neutralize both viruses, but had reduced potency against JRFL. Pinter2004 (variant cross-reactivity)
X5: Sera from two HIV+ people and a panel of MAbs were used to explore susceptibility to neutralization in the presence or absence of glycans within or adjacent to the V3 loop and within the C2, C4 and V5 regions of HIV-1 SF162 env gp120. The loss of the glycan within the V3 loop (GM299 V3) and two sites adjacent to V3, C2 (GM292 C2) and (GM329 C3), increased neutralization susceptibility to CD4i FAb X5, but each of the glycan mutants and SF162 were refractive to neutralization with 48d and 17b. The loss of sites in C4 (GM438 C4), or V5 (GM454 V5) did not increase neutralization susceptibility to FAb X5. V3 glycans tended to shield V3 loop, CD4 and co-receptor MAb binding sites, while C4 and V5 glycans shielded V3 loop, CD4, gp41 but not co-receptor MAb binding sites. Selective removal of glycans from a vaccine candidate may enable greater access to neutralization susceptible epitopes. McCaffrey2004 (antibody binding site, vaccine antigen design)
X5: The structure of the Fab X5 was determined at 1.9 angstrom resolution. The binding site is a long, 22 amino acid CDR H3 with a hook shape. Long CDR H3s are also found in IgG1b12 (18 residues) and 17b (19 residues). FAb X5 has a W100, F100Y in the CDR H3 hook shown to be important for binding through site specific mutagenesis. Compared to JRCSF, Ala substitutions at eight residues reduced binding more than 3 fold: C119, K207, G367, M426, W427, V430, I423, and K432. Only I423A and K432A were thought to possibly directly interact with X5, the other mutations were thought likely to disrupt the overall structure or CD4 binding. Darbha2004 (antibody binding site, structure)
X5: This review summarizes MAbs directed to HIV-1 Env. There are six CD4 inducible MAbs and Fabs in the database. The MAb forms neutralize TCLA strains only, but the smaller Fabs and scFv fragments can neutralize primary isolates. Gorny2003 (review)
X5: A gp120 molecule was designed to focus the immune response onto the IgG1b12 epitope. Ala substitutions that enhance the binding of IgG1b12 and reduce the binding of non-neutralizing MAbs were combined with additional N-linked glycosylation site sequons inhibiting binding of non-neutralizing MAbs; b12 bound to the mutated gp120. C1 and C5 were also removed, but this compromised b12 binding. Pantophlet2003b (vaccine antigen design)
X5: scFv 4KG5 reacts with a conformational epitope. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120. MAbs to the V2 loop, V3 loop, V3-C4 region, and CD4BS diminished binding, while MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected. This is a CD4i MAb that had no impact on 4KG5 binding. Zwick2003a (antibody interactions)
X5: The Fab m18 was selected from a human phage display library by a new method called sequential antigen panning (SAP), using a series of antigens to screen the library to pick broadly cross-reactive isolates. The ability to block cell mediated fusion by m18 was compared to Fabs X5 and b12 for a clade A, CRF01 EA, G, and 6 clade B isolates, and the inhibitory activity of m18 was slightly lower but comparable to neutralizing Fabs b12 and X5. It also showed broad cross-neutralization; 11/15 pseudotyped Envs from primary isolates from clades A-F were inhibited in an IC50 assay at concentration less than or equal to 100 ug/ml; X5 was also tested and somewhat more potent, generally requiring lower concentrations and inhibiting 13/15 primary isolates. Zhang2003 (variant cross-reactivity, subtype comparisons)
X5: This study shows the fragments of CD4i MAbs are better able to neutralize virus than whole IgG. Neutralization of HIV-1 R5 isolates JRFL, JR-CSF and ADA by CD4i MAbs X5, 17b, and 48d decreased with increased molecule size, the neutralizing potency of single-chain Fv (scFv) > than Fab fragments > whole Ab molecules. (With the exception of IgG 48d neutralization of HIV-1 ADA.) HIV-1 X4 isolates 89.6 and HxB2 are both relatively sensitive even to the larger IgG version. R5X4 isolate neutralization was dependent on the isolate and co-receptor usage. The CD4i MAb fragments neutralize HIV-1 subsequent to CD4 binding. The CD4i MAbs bind near the co-receptor binding sites on gp120. Co-receptors bind to the conserved beta19 strand and part of the V3 loop, regions that are masked by the V1V2 loops in the CD4-unbound state. When CD4 is bound, the co-receptor site is exposed near the membrane surface where it would be optimally accessible to co-receptors, and the smaller versions of the molecules are better able to overcome the steric hindrance. Labrijn2003 (antibody binding site, co-receptor, variant cross-reactivity)
X5: Called Fab X5. This paper is a study of the 2F5 NAb complexed to peptide ELDKWAS; the peptide was found to interact with amino acids near the base of the very long (22 residue) CDR 3H region of the Ab, although a Phe at the apex of the loop was also important. The authors suggest that particularly long CDR H3 regions may be a common feature of HIV-1 neutralizing antibodies -- there are 22 residues in 2F5's H3, 18 in b12's H3, and 22 residues in X5's H3. They express concern that because small animals like mice are unable to elicit Ab responses with such long H3s, they may be poor model systems for HIV vaccine studies. Zwick2004a (antibody interactions)
X5: The SOS mutant envelope protein introduces a covalent disulfide bond between gp120 surface and gp41 transmembrane proteins into the R5 isolate JR-FL by adding cysteines at residues 501 and 605. Pseudovirions bearing this protein bind to CD4 and co-receptor bearing cells, but do not fuse until treatment with a reducing agent, and are arrested prior to fusion after CD4 and co-receptor engagement. CD4i Abs X5 and 17b were weakly neutralizing in all formats, WT, SOS, and when added postbinding. Binley2003 (vaccine antigen design)
X5: The human Fab X5 was selected from a phage display library derived from an HIV-1 positive donor with a highly neutralizing serum -- it was selected for binding to purified gp120-CD4-coreceptor complexes -- the Fab neutralizes PBMC infection by a selection of HIV-1 primary isolates from clades A, B, C, D, E, F, and G, and neutralizes R5, X4, and R5X4 isolates -- it binds to a conserved epitope on gp120 induced by CD4 binding, its binding is slightly enhanced by CCR5 binding -- while CD4i MAb 17b binds the CCR5 binding site, X5 also competes with Fab b12 which overlaps with the CD4 binding site, suggesting the epitope for is near both the CD4 and CCR5 binding sites. Moulard2002 (antibody binding site, antibody generation, variant cross-reactivity, subtype comparisons)

References

Showing 68 of 68 references.

Isolation Paper
Moulard2002 Maxime Moulard, Sanjay K. Phogat, Yuuei Shu, Aran F. Labrijn, Xiaodong Xiao, James M. Binley, Mei-Yun Zhang, Igor A. Sidorov, Christopher C. Broder, James Robinson, Paul W. H. I. Parren, Dennis R. Burton, and Dimiter S. Dimitrov. Broadly Cross-Reactive HIV-1-Neutralizing Human Monoclonal Fab Selected for Binding to gp120-CD4-CCR5 Complexes. Proc. Natl. Acad. Sci. U.S.A., 99(10):6913-6918, 14 May 2002. PubMed ID: 11997472. Show all entries for this paper.

Acharya2013 Priyamvada Acharya, Timothy S. Luongo, Ivelin S. Georgiev, Julie Matz, Stephen D. Schmidt, Mark K. Louder, Pascal Kessler, Yongping Yang, Krisha McKee, Sijy O'Dell, Lei Chen, Daniel Baty, Patrick Chames, Loic Martin, John R. Mascola, and Peter D. Kwong. Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1 Neutralization by Recognizing a CD4-Induced Epitope That Includes Elements of Coreceptor- and CD4-Binding Sites. J. Virol., 87(18):10173-10181, Sep 2013. PubMed ID: 23843638. Show all entries for this paper.

Ali2016 Ayub Ali, Scott G . Kitchen, Irvin S.Y. Chen, Hwee L. Ng, Jerome A. Zack, and Otto O. Yang. HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies. J.Virol., 90(15):6999-7006, 1 Aug 2016. PubMed ID: 27226366. Show all entries for this paper.

Chen2009b Weizao Chen and Dimiter S. Dimitrov. Human Monoclonal Antibodies and Engineered Antibody Domains as HIV-1 Entry Inhibitors. Curr. Opin. HIV AIDS, 4(2):112-117, Mar 2009. PubMed ID: 19339949. Show all entries for this paper.

Choudhry2006 Vidita Choudhry, Mei-Yun Zhang, Ilia Harris, Igor A. Sidorov, Bang Vu, Antony S. Dimitrov, Timothy Fouts, and Dimiter S. Dimitrov. Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration. Biochem. Biophys. Res. Commun., 348(3):1107-1115, 29 Sep 2006. PubMed ID: 16904645. Show all entries for this paper.

Crooks2008 Emma T. Crooks, Pengfei Jiang, Michael Franti, Sharon Wong, Michael B. Zwick, James A. Hoxie, James E. Robinson, Penny L. Moore, and James M. Binley. Relationship of HIV-1 and SIV Envelope Glycoprotein Trimer Occupation and Neutralization. Virology, 377(2):364-378, 1 Aug 2008. PubMed ID: 18539308. Show all entries for this paper.

Darbha2004 Ramalakshmi Darbha, Sanjay Phogat, Aran F. Labrijn, Yuuei Shu, Yijun Gu, Michelle Andrykovitch, Mei-Yun Zhang, Ralph Pantophlet, Loic Martin, Claudio Vita, Dennis R. Burton, Dimiter S. Dimitrov, and Xinhua Ji. Crystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope. Biochemistry, 43(6):1410-1417, 17 Feb 2004. PubMed ID: 14769016. Show all entries for this paper.

DeVico2007 Anthony DeVico, Timothy Fouts, George K. Lewis, Robert C. Gallo, Karla Godfrey, Manhattan Charurat, Ilia Harris, Lindsey Galmin, and Ranajit Pal. Antibodies to CD4-Induced Sites in HIV gp120 Correlate with the Control of SHIV Challenge in Macaques Vaccinated with Subunit Immunogens. Proc. Natl. Acad. Sci. U.S.A., 104(44):17477-17482, 30 Oct 2007. PubMed ID: 17956985. Show all entries for this paper.

Falkowska2012 Emilia Falkowska, Alejandra Ramos, Yu Feng, Tongqing Zhou, Stephanie Moquin, Laura M. Walker, Xueling Wu, Michael S. Seaman, Terri Wrin, Peter D. Kwong, Richard T. Wyatt, John R. Mascola, Pascal Poignard, and Dennis R. Burton. PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4. J. Virol., 86(8):4394-4403, Apr 2012. PubMed ID: 22345481. Show all entries for this paper.

Haynes2010 Barton F. Haynes, Nathan I. Nicely, and S. Munir Alam. HIV-1 Autoreactive Antibodies: Are They Good or Bad for HIV-1 Prevention? Nat. Struct. Mol. Biol., 17(5):543-545, May 2010. PubMed ID: 20442740. Show all entries for this paper.

Joos2007 Beda Joos, Marek Fischer, Andreas Schweizer, Herbert Kuster, Jürg Böni, Joseph K. Wong, Rainer Weber, Alexandra Trkola, and Huldrych F. Günthard. Positive In Vivo Selection of the HIV-1 Envelope Protein gp120 Occurs at Surface-Exposed Regions. J. Infect. Dis., 196(2):313-320, 15 Jul 2007. PubMed ID: 17570120. Show all entries for this paper.

Labrijn2003 Aran F. Labrijn, Pascal Poignard, Aarti Raja, Michael B. Zwick, Karla Delgado, Michael Franti, James Binley, Veronique Vivona, Christoph Grundner, Chih-Chin Huang, Miro Venturi, Christos J. Petropoulos, Terri Wrin, Dimiter S. Dimitrov, James Robinson, Peter D. Kwong, Richard T. Wyatt, Joseph Sodroski, and Dennis R. Burton. Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol., 77(19):10557-10565, Oct 2003. PubMed ID: 12970440. Show all entries for this paper.

Leaman2010 Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658. Show all entries for this paper.

Liao2013a Hongyan Liao, Jun-tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, and Zhixin Zhang. Contribution of V(H) Replacement Products to the Generation of Anti-HIV Antibodies. Clin. Immunol., 146(1):46-55, Jan 2013. PubMed ID: 23220404. Show all entries for this paper.

Liu2008 Jun Liu, Alberto Bartesaghi, Mario J. Borgnia, Guillermo Sapiro, and Sriram Subramaniam. Molecular Architecture of Native HIV-1 gp120 Trimers. Nature, 455(7209):109-113, 4 Sep 2008. PubMed ID: 18668044. Show all entries for this paper.

Meyerson2013 Joel R. Meyerson, Erin E. H. Tran, Oleg Kuybeda, Weizao Chen, Dimiter S. Dimitrov, Andrea Gorlani, Theo Verrips, Jeffrey D. Lifson, and Sriram Subramaniam. Molecular Structures of Trimeric HIV-1 Env in Complex with Small Antibody Derivatives. Proc. Natl. Acad. Sci. U.S.A., 110(2):513-518, 8 Jan 2013. PubMed ID: 23267106. Show all entries for this paper.

Miller2005 Michael D. Miller, Romas Geleziunas, Elisabetta Bianchi, Simon Lennard, Renee Hrin, Hangchun Zhang, Meiqing Lu, Zhiqiang An, Paolo Ingallinella, Marco Finotto, Marco Mattu, Adam C. Finnefrock, David Bramhill, James Cook, Debra M. Eckert, Richard Hampton, Mayuri Patel, Stephen Jarantow, Joseph Joyce, Gennaro Ciliberto, Riccardo Cortese, Ping Lu, William Strohl, William Schleif, Michael McElhaugh, Steven Lane, Christopher Lloyd, David Lowe, Jane Osbourn, Tristan Vaughan, Emilio Emini, Gaetano Barbato, Peter S. Kim, Daria J. Hazuda, John W. Shiver, and Antonello Pessi. A Human Monoclonal Antibody Neutralizes Diverse HIV-1 Isolates By Binding a Critical gp41 Epitope. Proc. Natl. Acad. Sci. U.S.A., 102(41):14759-14764, 11 Oct 2005. PubMed ID: 16203977. Show all entries for this paper.

Narayan2013 Kristin M. Narayan, Nitish Agrawal, Sean X. Du, Janelle E. Muranaka, Katherine Bauer, Daniel P. Leaman, Pham Phung, Kay Limoli, Helen Chen, Rebecca I. Boenig, Terri Wrin, Michael B. Zwick, and Robert G. Whalen. Prime-boost immunization of rabbits with HIV-1 gp120 elicits potent neutralization activity against a primary viral isolate. PLoS One, 8(1):e52732 doi, 2013. PubMed ID: 23326351 Show all entries for this paper.

Nelson2008 Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton, and Michael B. Zwick. Antibody Elicited against the gp41 N-Heptad Repeat (NHR) Coiled-Coil Can Neutralize HIV-1 with Modest Potency but Non-Neutralizing Antibodies Also Bind to NHR Mimetics. Virology, 377(1):170-183, 20 Jul 2008. PubMed ID: 18499210. Show all entries for this paper.

Pancera2010a Marie Pancera, Shahzad Majeed, Yih-En Andrew Ban, Lei Chen, Chih-chin Huang, Leopold Kong, Young Do Kwon, Jonathan Stuckey, Tongqing Zhou, James E. Robinson, William R. Schief, Joseph Sodroski, Richard Wyatt, and Peter D. Kwong. Structure of HIV-1 gp120 with gp41-Interactive Region Reveals Layered Envelope Architecture and Basis of Conformational Mobility. Proc. Natl. Acad. Sci. U.S.A., 107(3):1166-1171, 19 Jan 2010. PubMed ID: 20080564. Show all entries for this paper.

Polonis2008 Victoria R. Polonis, Bruce K. Brown, Andrew Rosa Borges, Susan Zolla-Pazner, Dimiter S. Dimitrov, Mei-Yun Zhang, Susan W. Barnett, Ruth M. Ruprecht, Gabriella Scarlatti, Eva-Maria Fenyö, David C. Montefiori, Francine E. McCutchan, and Nelson L. Michael. Recent Advances in the Characterization of HIV-1 Neutralization Assays for Standardized Evaluation of the Antibody Response to Infection and Vaccination. Virology, 375(2):315-320, 5 Jun 2008. PubMed ID: 18367229. Show all entries for this paper.

Stanfield2005 Robyn L. Stanfield and Ian A. Wilson. Structural Studies of Human HIV-1 V3 Antibodies. Hum Antibodies, 14(3-4):73-80, 2005. PubMed ID: 16720977. Show all entries for this paper.

vonBredow2016 Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574. Show all entries for this paper.

Walker2010 Laura M. Walker, Melissa D. Simek, Frances Priddy, Johannes S. Gach, Denise Wagner, Michael B. Zwick, Sanjay K. Phogat, Pascal Poignard, and Dennis R. Burton. A Limited Number of Antibody Specificities Mediate Broad and Potent Serum Neutralization in Selected HIV-1 Infected Individuals. PLoS Pathog., 6(8), 2010. PubMed ID: 20700449. Show all entries for this paper.

Wen2010 Michael Wen, Reetakshi Arora, Huiqiang Wang, Lihong Liu, Jason T. Kimata, and Paul Zhou. GPI-Anchored Single Chain Fv---An Effective Way To Capture Transiently-Exposed Neutralization Epitopes on HIV-1 Envelope Spike. Retrovirology, 7:79, 2010. PubMed ID: 20923574. Show all entries for this paper.

Willey2008 Suzanne Willey and Marlén M. I. Aasa-Chapman. Humoral Immunity to HIV-1: Neutralisation and Antibody Effector Functions. Trends Microbiol., 16(12):596-604, Dec 2008. PubMed ID: 18964020. Show all entries for this paper.

Wu2011 Xueling Wu, Tongqing Zhou, Jiang Zhu, Baoshan Zhang, Ivelin Georgiev, Charlene Wang, Xuejun Chen, Nancy S. Longo, Mark Louder, Krisha McKee, Sijy O'Dell, Stephen Perfetto, Stephen D. Schmidt, Wei Shi, Lan Wu, Yongping Yang, Zhi-Yong Yang, Zhongjia Yang, Zhenhai Zhang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Melissa Simek, Dennis R. Burton, Wayne C. Koff, Nicole A. Doria-Rose, Mark Connors, NISC Comparative Sequencing Program, James C. Mullikin, Gary J. Nabel, Mario Roederer, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science, 333(6049):1593-1602, 16 Sep 2011. PubMed ID: 21835983. Show all entries for this paper.

Xiao2009 Xiaodong Xiao, Weizao Chen, Yang Feng, Zhongyu Zhu, Ponraj Prabakaran, Yanping Wang, Mei-Yun Zhang, Nancy S. Longo, and Dimiter S. Dimitrov. Germline-Like Predecessors of Broadly Neutralizing Antibodies Lack Measurable Binding to HIV-1 Envelope Glycoproteins: Implications for Evasion of Immune Responses and Design of Vaccine Immunogens. Biochem. Biophys. Res. Commun., 390(3):404-409, 18 Dec 2009. PubMed ID: 19748484. Show all entries for this paper.

Zhang2003 Mei-Yun Zhang, Yuuei Shu, Sanjay Phogat, Xiaodong Xiao, Fatim Cham, Peter Bouma, Anil Choudhary, Yan-Ru Feng, Inaki Sanz, Susanna Rybak, Christopher C. Broder, Gerald V. Quinnan, Thomas Evans, and Dimiter S. Dimitrov. Broadly Cross-Reactive HIV Neutralizing Human Monoclonal Antibody Fab Selected by Sequential Antigen Panning of a Phage Display Library. J. Immunol. Methods, 283(1-2):17-25, Dec 2003. PubMed ID: 14659896. Show all entries for this paper.

Zhang2007 Mei-Yun Zhang and Dimiter S. Dimitrov. Novel Approaches for Identification of Broadly Cross-Reactive HIV-1 Neutralizing Human Monoclonal Antibodies and Improvement of Their Potency. Curr. Pharm. Des., 13(2):203-212, 2007. PubMed ID: 17269928. Show all entries for this paper.

Zhang2010 Mei-Yun Zhang, Andrew Rosa Borges, Roger G. Ptak, Yanping Wang, Antony S. Dimitrov, S. Munir Alam, Lindsay Wieczorek, Peter Bouma, Timothy Fouts, Shibo Jiang, Victoria R. Polonis, Barton F. Haynes, Gerald V. Quinnan, David C. Montefiori, and Dimiter S. Dimitrov. Potent and Broad Neutralizing Activity of a Single Chain Antibody Fragment against Cell-Free and Cell-Associated HIV-1. mAbs, 2(3):266-274, May-Jun 2010. PubMed ID: 20305395. Show all entries for this paper.

Zhang2013 Yu Zhang, Tingting Yuan, Jingjing Li, Yanyu Zhang, Jianqing Xu, Yiming Shao, Zhiwei Chen, and Mei-Yun Zhang. The Potential of the Human Immune System to Develop Broadly Neutralizing HIV-1 Antibodies: Implications for Vaccine Development. AIDS, 27(16):2529-2539, 23 Oct 2013. PubMed ID: 24100711. Show all entries for this paper.

Zwick2004a Michael B. Zwick, H. Kiyomi Komori, Robyn L. Stanfield, Sarah Church, Meng Wang, Paul W. H. I. Parren, Renate Kunert, Hermann Katinger, Ian A. Wilson, and Dennis R. Burton. The Long Third Complementarity-Determining Region of the Heavy Chain is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5. J. Virol., 78(6):3155-3161, Mar 2004. PubMed ID: 14990736. Show all entries for this paper.

Displaying record number 1131

Download this epitope record as JSON.

MAb ID	39F (3.9F)
HXB2 Location	Env	Env Epitope Map
Author Location	gp120(gp120 )
Research Contact	James Robinson, Tulane University, New Orleans, LA, USA
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	no
Species (Isotype)	human(IgG1)
Patient	LTNP
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody interactions, assay or method development, binding affinity, co-receptor, enhancing activity, glycosylation, kinetics, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 39 of 39 notes.

39F: Lipid-based nanoparticles for the multivalent display of trimers have been shown to enhance humoral responses to trimer immunogens in the context of HIV vaccine development. After immunization with soluble MD39 SOSIP trimers (a stabilized version of BG505), trimer-conjugated liposomes improved both germinal center B cell and trimer-specific T follicular helper cell responses. In particular, MD39-liposomes showed high levels of binding by bNAbs such as V3 glycan specific PGT121, V1/V2 glycan specific PGT145, gp120/gp41 interface specific PGT151, CD4 binding site specific VRC01, and showed minimal binding by non-NAbs like CD4 binding site specific B6, and V3 specific 4025 or 39F. Tokatlian2018 (vaccine antigen design, binding affinity)
39F: The first cryo-EM structure of a cross-linked vaccine antigen was solved. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a bNAb PGV04 Fab fragment revealed how cross-linking affects key properties of the trimer. SOSIP and GLA-SOSIP trimers were compared for antigenicity by ELISA, using a large panel of mAbs previously determined to react with BG505 Env. Non-NAbs like 39F globally lost reactivity (7-fold median loss of binding), likely because of covalent stabilization of the cross-linked ‘closed’ form of the GLA-SOSIP trimer that binds non-NAbs weakly or not at all. V3-specific non-NAbs showed 2.1–3.3-fold reduced binding. Three autologous rabbit monoclonal NAbs to the N241/N289 ‘glycan-hole’ surface, showed a median ˜1.5-fold reduction in binding. V3 non-NAb 4025 showed residual binding to the GLA-SOSIP trimer. By contrast, bNAbs broadly retained reactivity significantly better than non-NAbs, with exception of PGT145 (3.3-5.3 fold loss of binding in ELISA and SPR). Schiffner2018 (vaccine antigen design, binding affinity, structure)
39F: SOSIP.664 trimer was modified at V3 positions 306 and 308 by Leucine substitution to create hydrophobic interactions with the tryptophan residue at position 316 and the V1V2 domain. These modifications stabilized the resulting SOSIP.v5.2 S306L R308L trimers. In vivo, the induction of V3 non-NAbs was significantly reduced compared with the SOSIP.v5.2 trimers. With S306L plus R308L substitutions, 39F did not bind to SOSIP.v5.2 and SOSIP.v5.2 constructs deTaeye2018 (antibody binding site, binding affinity)
39F: Three strategies were applied to perturb the structure of Env in order to make the protein more susceptible to neutralization: exposure to cold, Env-activating ligands, and a chaotropic agent. A panel of mAbs (E51, 48d, 17b, 3BNC176, 19b, 447-52D, 39F, b12, b6, PG16, PGT145, PGT126, 35O22, F240, 10E8, 7b2, 2G12) was used to test the neutralization resistance of a panel of subtype B and C pseudoviruses with and without these agents. Both cold and CD4 mimicking agents (CD4Ms) increased the sensitivity of some viruses. The chaotropic agent urea had little effect by itself, but could enhance the effects of cold or CD4Ms. Thus Env destabilizing agents can make Env more susceptible to neutralization and may hold promise as priming vaccine antigens. Johnson2017 (vaccine antigen design)
3.9F: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson.
39F: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120.N197 glycan mutants were tested against 39F showing a loss of tier 2 phenotype. The results are in Table S5. Crooks2015 (glycosylation, neutralization)
39F: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41_ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC₅₀ >50µg/ml). Pugach2015
39F: Two clade C recombinant Env glycoprotein trimers, DU422 and ZM197M, with native-like structural and antigenic properties involving epitopes for all known classes of bNAbs, were produced and characterized. These Clade C trimers (10-15% of which are in a partially open form) were more like B41 Clade B trimers which have 50-75% trimers in the partially open configuration than like B505 Clade B trimers, almost 100% in the closed, prefusion state. Clade C ZM197M trimer had low binding affinity to anti-V3 Ab 39F, while the DU422 trimer as well as both trimer-pseudotyped viruses did not bind 39F and were not neutralized by it either. Julien2015 (assay or method development, structure)
39F: Env trimer BG505 SOSIP.664 as well as the clade B trimer B41 SOSIP.664 were stabilized using a bifunctional aldehyde (glutaraldehye, GLA) or a heterobifunctional cross-linker, EDC/NHS with modest effects on antigenicity and barely any on biochemistry or structural morphology. ELISA, DSC and SPR were used to test recognition of the trimers by bNAbs, which was preserved and by weakly NAbs or non-NAbs, which was reduced. Cross-linking partially preserves quaternary morphology so that affinity chromatography by positive selection using quaternary epitope-specific bNAabs, and negative selection using non-NAbs, enriched antigenic characteristics of the trimers. Binding of anti-V3 non-NAb 39F to trimers was reduced by trimer cross-linking. Schiffner2016 (assay or method development, binding affinity, structure)
39F: A new trimeric immunogen, BG505 SOSIP.664 gp140, was developed that bound and activated most known neutralizing antibodies but generally did not bind antibodies lacking neuralizing activity. This highly stable immunogen mimics the Env spike of subtype A transmitted/founder (T/F) HIV-1 strain, BG505. Anti-V3 non-NAb 39F did not neutralize BG505.T332N, the pseudoviral equivalent of the immunogen BG505 SOSIP.664 gp140, but did recognize and bind the immunogen itself. Sanders2013 (assay or method development, neutralization, binding affinity)
39F: The study's goal was to produce modified SOSIP trimers that would reduce the exposure - and, by inference, the immunogenicity - of non-NAb epitopes such as V3. The binding of several modified SOSIP trimers was compared among 12 neutralizing (PG9, PG16, PGT145, PGT121, PGT126, 2G12, PGT135, VRC01, CH103, CD4, IgG2, PGT151, 35O22) and 3 non-neutralizing antibodies (14e, 19b, b6). The V3 non-NAbs 447-52D, 39F, 14e, and 19b bound less well to all A316W variant trimers compared to wild-type trimers. Mice and rabbits immunized with modified, stabilized SOSIP trimers developed fewer V3 Ab responses than those immunized with native trimers. deTaeye2015 (antibody binding site)
39F: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". 39F was used in the anti-gp120 cocktail in BN-PAGE and western blot experiments to prove that enzymes removed junk Env from VLPs and inactivated virus.. Crooks2011 (glycosylation)
39F: NIH AIDS Reagent program Catalog# 11437. Derived by EBV transformation of B cells from PBMCs of an asymptomatic HIV-1 infected patient. Antibody binds to a linear epitope involving the N-terminal side of the V3 loop. 39F neutralizes a small proportion of HIV-1 Clade B primary isolates.
39F: The goal of this study was to improve the humoral response to HIV-1 by targeting trimeric Env gp140 to B cells. The gp140 was fused to a proliferation-inducing ligand (APRIL), B cell activation factor (BAFF) and CD40 ligand (CD40L). These fusion proteins increased the expression of activation-induced-cytidine deaminase (AID) responsible for somatic hypermutation, Ab affinity maturation, and Ab class switching. The Env-APRIL induced high anti-Env responses against tier1 viruses. 39F was used in BN-PAGE trimer shift assay. Melchers2012 (neutralization)
39F: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. 39F was used as a control mAb in the comprehensive set of assays performed. Tomaras2011 (neutralization, polyclonal antibodies)
39F: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding of 39F to WT VLPs is consistent with the recognition of non-functional Env. 39F recognized UNC WT VLPs far more than WT VLPs but did not neutralize trimer VLPs. Tong2012 (neutralization, binding affinity)
39F: To improve the immunogenicity of HIV-1 Env vaccines, a chimeric gp140 trimer in which V1V2 region was replaced by the GM-CSF cytokine was constructed. We selected GM-CSF was selected because of its defined adjuvant activity. Chimeric EnvGM-CSF protein enhanced Env-specific Ab and T cell responses in mice compared with wild-type Env. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. 3 proteins were studied: Env-wild-type, Env-ΔV1V2, Env-hGM-CSF. V3 MAb 39F recognized the three Env proteins equally well. vanMontfort2011 (vaccine antigen design)
39F: The antigenic structure of Gag-Env pseudovirions was characterized and it was shown that these particles can recapitulate native HIV virion epitope structures. 39F hybridoma cell line was shown to specifically recognize the Gag-Env pseudovirions. The Gag-Env pseudovirions were further used to identify a subset of antigen-specific B cells in chronically infected HIV subjects. Hicar2010 (binding affinity, structure)
39F: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. 39F bound better to all uncleaved ΔV1V2 variants than to the full-length trimer, indicating better exposure of the 39F epitope when V1V2 domain is removed. Bontjer2010 (antibody binding site, binding affinity)
39F: GnTI virus (complex glycans of the neutralizing face are replaced by fully trimmed oligomannose stumps), and the N301Q mutant virus (glycan at position 301 is removed), were both significantly more sensitive to neutralization by 39F compared to the parental virus. This suggests that the antennae of the complex glycans play a significant role in protecting the V3 loop from Ab binding. Removal of terminal sialic acids on complex glycans by neuraminidase treatment did not affect virus susceptibility to 39F. 39F did not bind to native Env trimers. Binley2010 (glycosylation, neutralization, binding affinity)
3.9F: This human Ab was compared to the Abs derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 2909 and IgGb12. 3.9F captured SF162, SF162ΔV1, and SF162ΔV2 but did not capture ΔV3 virions. Robinson2010 (binding affinity)
39F: Resurfaced stabilized core 3 (RSC3) protein was designed to preserve the antigenic structure of the gp120 CD4bs neutralizing surface but eliminate other antigenic regions of HIV-1. RSC3 did not show binding to 39F. Wu2010 (binding affinity)
39F: Sera from both gp120 DNA prime-protein boost immunized rabbits and from protein-only immunized rabbits competed for binding to 39F, indicating elicitation of 39F-like Abs by both immunization regimens. Competitive virus capture assay revealed higher titers of 39F-like Abs in animals immunized with DNA prime-protein boost than in protein-only immunized animals. Vaine2008 (vaccine antigen design)
39F: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by 39F, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive for neutralization by 39F, although 39F bound strongly to gp120 from CC1/85. These results indicate that V3-dependent and -independent changes responsible for CCR5 inhibitor resistance do not necessarily alter the exposure of V3 to some of the V3 Abs. Pugach2008 (co-receptor, neutralization, binding affinity)
39F: 39F neutralized two of the 15 subtype B isolates tested, 93TH305 and 92BR020c. Binding affinity of MAb 39F to gp120 was strongly reduced upon substitutions of Lys305 or Ile307 to Ala, and was moderately reduced upon substitutions of Ser306 and Ile309. Substitutions of Arg298 or Arg304 also diminished binding but not substantially, indicating that 39F interacts principally with the N-terminal flank of the V3 loop. Of the 13 viruses that were not neutralized by 39F, the resistance of 6 viruses could be explained by substitutions at important contact residues, while neutralization resistance of 7 viruses could not be explained by this. The fine specificity of 39F was mapped onto V3 in the structural context of gp120. Residues Lys305, Ser306, Ile307, and Ile309 form a distinct binding site on the N-terminal flank of V3, supporting the indication that 39F interacts with the N-terminal part of V3. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
39F: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. V3 Ab activity was measured by the abilities of the plasmas to inhibit capture of JR-FL virus particles by 39F. Modest titers were exhibited by subtype B plasmas, while subtype C plasmas showed lower activities, suggesting subtype-specific V3 loop binding. Binley2008 (neutralization, subtype comparisons)
39F: This review summarizes data on the development of HIV-1 centralized genes (consensus and ancestral) for induction of neutralizing antibody responses. Functionality and conformation of native epitopes in proteins based on the centralized genes was tested and confirmed by binding to 39F and other MAbs. Gao2007 (antibody binding site, review)
39F: Guinea pigs were immunized with gp120 protein, or with three types of VLPs containing disulfide-shackled functional trimers (SOS-VLP), uncleaved nonfunctional Env (UNC-VLP), naked VLP bearing no Env. 39F was used in a capture assay showing that most of the SOS-VLP and UNC-VLP sera contained high titers of anti-V3 Abs. gp120 sera showed only moderate titers of V3 competing Abs. Crooks2007 (neutralization)
39F: Interactions of this Ab with gp120 monomer and two cleavage-defective gp140 trimers were studied. It was shown that 39F interactions with the soluble monomers and trimers were minimally affected by GA cross-linking of the proteins, indicating that the 39F epitope was maintained after cross-linking. This Ab was associated with a small entropy change upon gp120 binding. This Ab was shown to have a kinetic advantage as it bound to gp120 faster than other less neutralizing Abs. 39F successfully recognized untreated trimers and monomer expressed on cell surfaces but this recognition was decreased by cross-linking indicating that differences exist between the soluble trimers and native proteins. Yuan2006 (antibody binding site, antibody interactions, kinetics, binding affinity)
39F: A stable trimerization motif, GCN4, was appended to the C terminus of YU2gp120 to obtain stable gp120 trimers (gp120-GCN4). Each trimer subunit was capable of binding IgG1b12, indicating that they were at least 85% active. D457V mutation in the CD4 binding site resulted in a decreased affinity of the gp120-GCN4 for CD4, but the mutation did not affect binding of 39F. 39F was able to bind to both wildtype gp120, gp120-GCN4, and to the respective corresponding mutant molecules D457Vgp120 and D457Vgp120-GCN4 with the similar affinities. Pancera2005a (binding affinity)
39F: R-FL and YU2 HIV-1 strains were not neutralized by39F. 39F and other non-neutralizing Abs only recognized JR-FL cleavage-defective glycoproteins, while the neutralizing Abs (2G12 and IgG1b12) recognized both cleavage competent and cleavage-defective glycoproteins. It is suggested that an inefficient env glycoprotein precursor cleavage exposes non-neutralizing determinants, while only neutralizing regions remain accessible on efficiently cleaved spikes. For YU2, both cleavage-competent and -defective glycoproteins were recognized by both neutralizing and non-neutralizing Abs. 39F, along with other Abs able to neutralize lab-adapted isolates, displayed enhanced viral entry at higher Ab concentrations, whereas the Abs that cannot neutralize any virus did not display such enhancement. Pancera2005 (antibody binding site, enhancing activity, neutralization, binding affinity)
39F: CXCR4-using HXBc2 strain and CCR5-using YU2 strain differed from each other in amino acid residues 325 and 326 at the base of the V3 loop. Changing the residues 325 and 326 in the HXBc2 from the amino acids predominant in the CXCR4-using strains to amino acids predominant in the CCR5-using strains did not result in binding of 39F to HXBc2. Xiang2005 (antibody binding site, co-receptor)
39F: 29 subtype B V3 peptides were designed and used for immunization of guinea pigs. Peptides that induced Abs that neutralized more than 3 HIV isolates were shown to bind to this Ab better than peptides unable to induce neutralization of any of the HIV-1 primary isolates. Haynes2006 (neutralization, binding affinity)
39F: The gp140δCFI protein of CON-S M group consensus protein and gp140CFI and gp140CF proteins of CON6 and WT viruses from HIV-1 subtypes A, B and C were expressed in recombinant vaccinia viruses and tested as immunogens in guinea pigs. 39F was shown to bind specifically to all recombinant proteins except for the gp140δFI derived from subtype C virus. The specific binding of this Ab to CON-S indicated that its conformational epitope was intact. 39F also bound specifically to the two subtype B gp120 proteins tested. Liao2006 (antibody binding site, vaccine antigen design, subtype comparisons)
39F: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened, while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO. Selvarajah2005 (vaccine antigen design, vaccine-induced immune responses)
39F: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including 39F. To inhibit 39F binding, Arg 304 and Lys 305 had to be changed to Ala. Pantophlet2004 (vaccine antigen design)
39F: Thermodynamics of binding to gp120 was measured using isothermal titration calorimetry for sCD4, 17b, b12, 48d, F105, 2G12 and C11 to intact YU2 and the HXBc2 core. The free energy of binding was similar, and not only CD4 but MAb ligands induced thermodynamic changes in gp120 that were independent of whether the core or the full gp120 protein was used. Non-neutralizing CD4BS and CD4i MAbs had large entropy contributions to free energy (mean: 26.1 kcal/mol) of binding to the gp120 monomer, except the potent CD4BS neutralizing MAb b6 had a much smaller value of 5.7 kcal/mol. High values suggest surface burial or protein folding and ordering of amino acids. Variable loop MAbs (L17, L78, 19b, 39F, Ag1211, D0142, and G3-2999) MAbs that bind to the N and C termini (211/c, A32, L100, P35, and C11) do not have dramatic entropy changes. These results suggest that while the trimeric Env complex has four surfaces, a non-neutralizing face (occluded on the oligomer), a variable face, a neutralizing face and a silent face (protected by carbohydrate masking), gp120 monomers further protect receptor binding sites by conformational or entropic masking, requiring a large energy handicap for Ab binding not faced by other anti-gp120 Abs. Kwong2002 (antibody binding site)
39F: HIV-1 gp160deltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins from R5 strains YU2 and JRFL, and X4 strain HXBc2, were made in a physiologic membrane setting as candidate immunogens for HIV vaccines -- 2F5 bound to gp160deltaCT with a reconstituted membrane ten-fold better than the same protein on beads -- anti-CD4BS MAbs IgG1b12 and F105, A32 (C1-C4), C11 (C1-C5), and 39F (V3) MAbs bound gp160deltaCT PLs indistinguishably from gp160deltaCT expressed on the cell surface. Grundner2002
39F: Uncleaved soluble gp140 (YU2 strain, R5 primary isolate) can be stabilized in an oligomer by fusion with a C-term trimeric GCN4 motif or using a T4 trimeric motif derived from T4 bacteriophage fibritin -- stabilized oligomer gp140 delta683(-FT) showed strong preferential recognition by NAbs IgG1b12 and 2G12 relative to the gp120 monomer, in contrast to poorly neutralizing MAbs F105, F91, 17b, 48d, and 39F which showed reduced levels of binding, and C11, A32, and 30D which did not bind the stabilized oligomer. Yang2002

References

Showing 37 of 37 references.

Crooks2015 Ema T. Crooks, Tommy Tong, Bimal Chakrabarti, Kristin Narayan, Ivelin S. Georgiev, Sergey Menis, Xiaoxing Huang, Daniel Kulp, Keiko Osawa, Janelle Muranaka, Guillaume Stewart-Jones, Joanne Destefano, Sijy O'Dell, Celia LaBranche, James E. Robinson, David C. Montefiori, Krisha McKee, Sean X. Du, Nicole Doria-Rose, Peter D. Kwong, John R. Mascola, Ping Zhu, William R. Schief, Richard T. Wyatt, Robert G. Whalen, and James M. Binley. Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site. PLoS Pathog, 11(5):e1004932, May 2015. PubMed ID: 26023780. Show all entries for this paper.

Grundner2002 Christoph Grundner, Tajib Mirzabekov, Joseph Sodroski, and Richard Wyatt. Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins. J. Virol., 76(7):3511-3521, Apr 2002. PubMed ID: 11884575. Show all entries for this paper.

Melchers2012 Mark Melchers, Ilja Bontjer, Tommy Tong, Nancy P. Y. Chung, Per Johan Klasse, Dirk Eggink, David C. Montefiori, Maurizio Gentile, Andrea Cerutti, William C. Olson, Ben Berkhout, James M. Binley, John P. Moore, and Rogier W. Sanders. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses. J. Virol., 86(5):2488-2500, Mar 2012. PubMed ID: 22205734. Show all entries for this paper.

Pancera2005 Marie Pancera and Richard Wyatt. Selective Recognition of Oligomeric HIV-1 Primary Isolate Envelope Glycoproteins by Potently Neutralizing Ligands Requires Efficient Precursor Cleavage. Virology, 332(1):145-156, 5 Feb 2005. PubMed ID: 15661147. Show all entries for this paper.

Pancera2005a Marie Pancera, Jacob Lebowitz, Arne Schön, Ping Zhu, Ernesto Freire, Peter D. Kwong, Kenneth H. Roux, Joseph Sodroski, and Richard Wyatt. Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis. J. Virol., 79(15):9954-9969, Aug 2005. PubMed ID: 16014956. Show all entries for this paper.

Tokatlian2018 Talar Tokatlian, Daniel W. Kulp, Andrew A. Mutafyan, Christopher A. Jones, Sergey Menis, Erik Georgeson, Mike Kubitz, Michael H. Zhang, Mariane B. Melo, Murillo Silva, Dong Soo Yun, William R. Schief, and Darrell J. Irvine. Enhancing Humoral Responses Against HIV Envelope Trimers via Nanoparticle Delivery with Stabilized Synthetic Liposomes. Sci. Rep., 8(1):16527, 8 Nov 2018. PubMed ID: 30410003. Show all entries for this paper.

vanMontfort2011 Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R. Schief, John P. Moore, and Rogier W. Sanders. A Chimeric HIV-1 Envelope Glycoprotein Trimer with an Embedded Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Domain Induces Enhanced Antibody and T Cell Responses. J. Biol. Chem., 286(25):22250-22261, 24 Jun 2011. PubMed ID: 21515681. Show all entries for this paper.

Xiang2005 Shi-Hua Xiang, Michael Farzan, Zhihai Si, Navid Madani, Liping Wang, Eric Rosenberg, James Robinson, and Joseph Sodroski. Functional Mimicry of a Human Immunodeficiency Virus Type 1 Coreceptor by a Neutralizing Monoclonal Antibody. J. Virol., 79(10):6068-6077, May 2005. PubMed ID: 15857992. Show all entries for this paper.

Yang2002 Xinzhen Yang, Juliette Lee, Erin M. Mahony, Peter D. Kwong, Richard Wyatt, and Joseph Sodroski. Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin. J. Virol., 76(9):4634-4642, 1 May 2002. PubMed ID: 11932429. Show all entries for this paper.

Yuan2006 Wen Yuan, Jessica Bazick, and Joseph Sodroski. Characterization of the Multiple Conformational States of Free Monomeric and Trimeric Human Immunodeficiency Virus Envelope Glycoproteins after Fixation by Cross-Linker. J. Virol., 80(14):6725-6737, Jul 2006. PubMed ID: 16809278. Show all entries for this paper.

Displaying record number 1378

Download this epitope record as JSON.

MAb ID	CO11 (Co11)
HXB2 Location	Env	Env Epitope Map
Author Location	gp120 (V3)
Research Contact	James Robinson, Tulane University, New Orleans, LA, USA
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing
Species (Isotype)	human
Patient	AC-01
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, assay or method development, binding affinity, glycosylation, HAART, ART, neutralization, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity

Notes

Showing 11 of 11 notes.

CO11: LANL database note: This monoclonal antibody is a CHAVI reagent (http://chavi.org/); Species: human; Category: V3 MAbs; Contact person: James Robinson
CO11: This study investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit NAbs. Rabbits were immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). N197 glycan- and residue 230- removal conferred sensitivity to Trimer VLP sera and DNA trimer sera respectively, showing for the first time that strain-specific holes in the "glycan fence" can allow the development of tier 2 NAbs to native spikes. All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. All of the functional clones resisted neutralization by the V3 loop-specific mAb CO11, suggesting that they retain a tier 2 phenotype. Crooks2015 (glycosylation, neutralization)
CO11: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664, that exists in two conformations, closed and partially open. bNAbs tested against the trimer were able to neutralize the B41 pseudovirus with a wide range of potencies. Among non-NAbs to CD4bs (b6, F91, F105); to CD4i (17b); to gp41_ECTO (F240); and to V3 (447-52D, 39F, CO11, 19b and 14e), none neutralized B41 (IC₅₀ >50µg/ml). Pugach2015
CO11: This paper reported the nature of junk Env glycan that undermine the development of Ab responses against gp120/gp41 trimers and evaluated enzyme digestion as a way to remove aberrant Env to produce "trimer VLPs". Co11 was used in the anti-gp120 cocktail in the western blot experiment to prove that enzymes removed junk Env from VLPs and inactivated virus. Crooks2011 (glycosylation)
CO11: Antigenic properties of undigested VLPs and endo H-digested WT trimer VLPs were compared. Binding of CO11 to WT VLPs is consistent with the recognition of non-functional Env. CO11 recognized UNC WT VLPs far more than WT VLPs. CO11 did not neutralize trimer VLPs. BN-PAGE shifts using digested E168K + N189A WT trimer VLPs exhibited prominence and produced a high-molecular weight-complex compared to WT VLPs. Tong2012 (neutralization, binding affinity)
CO11: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. Using an ELISA assay, it was shown that the V3 epitope for CO11 Ab was lost on the CC101.19 compared to the parental virus gp120. Berro2009
CO11: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. CO11 belonged to the group 3 MAbs, which are able to bind subtype B but not subtype C gp120 and V3 peptide. CO11 was able to bind subtype B V3 in the subtype C Env backbone chimera, but not the reverse, indicating that CO11 binds to a structure created by the subtype B V3 sequence that is not impacted by the gp120 backbone. For both subtypes B and C, CO11 required H13 and R18 residues in order to bind, indicating that these residues likely define key aspects of the Ab epitope. CO11 was not able to neutralize JR-FL or SF162 isolates, but a chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by this Ab. Patel2008 (neutralization, binding affinity, subtype comparisons)
CO11: CO11 neutralized two of the 15 subtype B isolates tested, 93TH305 and 92BR020c. Binding affinity of MAb CO11 to gp120 was strongly reduced upon substitutions of His308, Pro313 (500-fold), or Arg315 to Ala. The dependence on Pro313 suggests that a precise conformation of the V3 β hairpin turn may be critical for binding of CO11. Thus, CO11 may need to interact with V3 from an angle, which does not permit access to V3 on many different primary viruses. CO11 inability to neutralize 6 of the 15 viruses tested could not be explained by substitution of important contact residues. The fine specificity of CO11 was mapped onto V3 in the structural context of gp120. This showed that the residues important for CO11 binding form a somewhat disjointed pattern, and that CO11 likely also contacts neighboring residues. Pantophlet2008 (antibody binding site, neutralization, variant cross-reactivity, binding affinity, structure)
CO11: A reverse capture assay was developed to assess what kind of human MAbs were produced in EBV B-cell transformation assays performed on PBMC sampled at different time-points from three HIV-1 infected patients on HAART. The reverse capture assay was validated by the solid phase MAbs that could not capture biotin-MAbs of the same or overlapping specificity when reacted with patient virus envelope glycoproteins preincubated with or without sCD4. Reverse capture assay showed that the produced Abs from the patients were able to block binding of biotin-labeled CO11, however the blocking was low, indicating presence of relatively few V3-binding Abs. Robinson2005 (antibody generation, assay or method development, HAART, ART)
CO11: Of 35 Env-specific MAbs tested, only 2F5, 4E10, IgG1b12, and two CD4BS adjacent MAbs (A32 and 1.4G) and gp41 MAbs (2.2B and KU32) had binding patterns suggesting polyspecific autoreactivity, and similar reactivities may be difficult to induce with vaccines because of elimination of such autoreactivity. CO11 has no indication of polyspecific autoreactivity. Haynes2005 (antibody binding site)
CO11: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only 3 additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including CO11. Pantophlet2004 (vaccine antigen design)

References

Showing 11 of 11 references.

Robinson2005 James E. Robinson, Debra Holton Elliott, Effie A. Martin, Kathryne Micken, and Eric S. Rosenberg. High Frequencies of Antibody Responses to CD4 Induced Epitopes in HIV Infected Patients Started on HAART during Acute Infection. Hum Antibodies, 14(3-4):115-121, 2005. PubMed ID: 16720981. Show all entries for this paper.

Displaying record number 1379

Download this epitope record as JSON.

MAb ID	F425 B4e8 (F425-B4e8, F425, F425b, B4e8, F425B4e8)
HXB2 Location	Env	Env Epitope Map
Author Location	gp120 (V3)
Research Contact	Lisa Cavacini, Beth Isreal Deconess Medical Center, Boston MA, USA
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG2κ)
Patient
Immunogen	HIV-1 infection
Keywords	acute/early infection, adjuvant comparison, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, binding affinity, co-receptor, dendritic cells, escape, glycosylation, HIV-2, neutralization, polyclonal antibodies, review, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 39 of 39 notes.

F425 B4e8: Rabbits were immunized with a DNA vaccine encoding JR-CSF gp120. Five sera with potent autologous neutralizing activity were selected and compared with a human neutralizing plasma (Z23) and monoclonal antibodies targeting various regions of gp120 (VRC01, b12, b6, F425, 2F5, 2G12, and X5). The rabbit sera contained different neutralizing activities dependent on C3 and V5, C3 and V4, or V4 regions of the glycan-rich outer domain of gp120. All sera showed enhanced neutralizing activity toward an Env variant that lacked a glycosylation site in V4. The JR-CSF gp120 epitopes recognized by the sera were distinct from those of the mAbs. The activity of one serum required specific glycans that are also important for 2G12 neutralization, and this serum blocked the binding of 2G12 to gp120. The findings show that different fine specificities can achieve potent neutralization of HIV-1, yet this strong activity does not result in improved breadth. Narayan2013 (neutralization, polyclonal antibodies)
F425-B4e8: The neutralization profile of 1F7, a human CD4bs mAb, is reported and compared to other bnNAbs. F425-B4e8 was used as a negative control to ΔV3 construct in several assays to characterize 1F7 binding. Gach2013 (neutralization)
B4e8: The strategy of incorporating extra glycans onto gp120 was explored, with the goal to occlude the epitopes of non-neutralizing MAbs while maintaining exposure of the b12 site. The focus was on the head-to-head comparison of the ability of 2 adjuvants, monophosphoryl lipid A (MPL) and Quil A, to promote CD4-specific Ab responses in mice immunized with the engineered mutant Q105N compared to gp120wt. Neutralizing and non-neutralizing antibodies targeting three areas on gp120 – the CD4bs (F105, b6, b12, b13, VRC01, VRC03 and CD4- IgG2), the glycosylated ‘silent face’ (2G12) and the V3 loop (B4e8) – were assessed for binding. The antibodies b6, b12, b13, VRC01 and 2G12 bound best to mutant Q105N, albeit with lower affinities than to gp120wt. Retention of b6 and b13 binding was not expected, but can be explained by their very similar mode of interaction with the CD4bs compared to b12. Abs F105 and VRC03 did not bind Q105N at all. The V3-specific antibody B4e8 did not bind to Q105N. Ahmed2012 (adjuvant comparison, antibody binding site, glycosylation, neutralization, escape)
B4e8: B4e8 neutralized 7 of the 15 subtype B isolates tested, of which 6 were resistant to neutralization by MAbs 19b, 39F, CO11, F2A3, F530, LA21 and LE311. Angle of interaction between B4e8 and V3 was shown by superimposing the Fab fragment of the Ab with V3. B4e8 was shown to interact with V3 from a slightly elevated angle relative to the MAbs 58.2 and 447-52D. Pantophlet2008 (antibody binding site, neutralization, structure)
B4e8: The crystal structure of the B4e8 Fab fragment in complex with a 24-mer V3 peptide (RP142) at 2.8 A resolution is described. B4e8 recognizes a novel V3 loop conformation, featuring a five-residue alpha-turn around the conserved GPGRA apex of the beta-hairpin loop and interacts primarily with V3 through side-chain contacts with just two residues, Ile(P309) and Arg(P315), while the remaining contacts are to the main chain. The structure can explain how B4e8 can tolerate a certain degree of sequence variation within V3 and, hence, is able to neutralize different HIV-1 isolates. Bell2008 (variant cross-reactivity, structure)
B4e8: The epitope for the MAb D19 is conserved and embedded in V3. D19 is unique in that for R5 viruses, it was cryptic and did not bind without exposure to sCD4, and for X4 and R5X4 isolates it was constitutively exposed. It had an overlapping binding region with MAbs 447-52D, B4e8, and 268-D, but different reactivity patterns and fine specificity. While B4e8 and 447-52D could bind to the R5 virus BaL in the absence of sCD4, treatment with sCD4 did increase the binding of both B4e8 and 447-52D, but did not impact their ability to neutralize BaL. Lusso2005 (antibody binding site)
B4e8: Called F425 B4e8. scFv 4KG5 reacts with a conformational epitope that is formed by the V1V2 and V3 loops and the bridging sheet (C4) region of gp120 and is influenced by carbohydrates. Of a panel of MAbs tested, only NAb b12 enhanced 4KG5 binding to gp120 JRFL. MAbs to the following regions diminished 4KG5 binding: V2 loop, V3 loop, V3-C4 region, CD4BS. MAbs directed against C1, CD4i, C5 regions didn't impact 4KG5 binding. These results suggest that the orientation or dynamics of the V1/V2 and V3 loops restricts CD4BS access on the envelope spike, and IgG1b12 can uniquely remain unaffected by these loops. This was one of the V3 MAbs used. Zwick2003a (antibody interactions)
B4e8: The effect of isotype (IgG1 and IgG3) and subtype (IgA) switching of parental F425B4e8 (IgG2)on HIV-1 binding and neutralization was investigated. IgG1-and IgA-F425B4e8 mutants showed virus-specific binding levels and TCLA SF2 isolate compared to the parental IgG2. Comparable levels of neutralization of primary isolates 92HT593 (R5X4) and 92US660 (R5) was achieved by all isotypes and subtypes of F425B4e8. Liu2003 (variant cross-reactivity, antibody sequence)
B4e8: This MAb binds to the base of the V3 loop, and binds and neutralizes multiple primary isolates. The anti-V3 MAb B4a1 cross-competes with B4e8. B4e8 and 2G12 enhanced each other's binding, and gave synergistic neutralization. B4e8 could neutralize R5X4 virus 92HT593 better than 2G12, while 2G12 was better at neutralizing R5 virus 92US660. B4e8 enhanced binding of CD4i MAbs 4.8d, 1.7b, and A1g8 to 92HT593, but only of 48d to the 92US660, and there was only a modest impact of the combination of B4e8 and CD4i MAbs on neutralization. CD4BS MAb IgG1b12 had no effect on B4e8 binding. Anti-gp41 MAb F240 inhibited B4e8 neutralization. Cavacini2003 (antibody binding site, antibody generation, antibody interactions, co-receptor, variant cross-reactivity)
F425-B4e8: Somatic hypermutations are preferably found in CDR loops, which alter the Ab combining sites, but not the overall structure of the variable domain. FWR of CDR are usually resistant to and less tolerant of mutations. This study reports that most bnAbs require somatic mutations in the FWRs which provide flexibility, increasing Ab breadth and potency. To determine the consequence of FWR mutations the framework residues were reverted to the Ab's germline counterpart (FWR-GL) and binding and neutralizing properties were then evaluated. F425-B4e8 was used in comparing the Ab framework amino acid replacement vs. interactive surface area on Ab. Klein2013 (neutralization, structure, antibody lineage)
F425B4e8: Role of CH1 heavy chain of 2F5 in Ag binding was reported. 2F5IgA2 containing CH1 was constructed and compared for binding affinity and functional activities. F425B4e8 was used to create a panel of antibodies specific for the V3 loop. Tudor2012 (neutralization, binding affinity, antibody sequence)
F425: Polyclonal B cell responses to conserved neutralization epitopes are reported. Cross-reactive plasma samples were identified and evaluated from 308 subjects tested. F425 was used as a control mAb in the comprehensive set of assays performed. Tomaras2011 (neutralization, polyclonal antibodies)
F425-B4e8: An additive effect between several NABs (MAb 126-7, MAb F425-B428 and gp120 antiserum) and silver nanoparticles (AgNPs) was seen when combined against HIV-1 infection in vitro. The addition of AgNPs to NABs has significantly increased the neutralizing potency of NABs in prevention of cell-associated HIV-1 transmission/infection. Lara2011 (antibody interactions)
F425 B4e8: To test whether HIV-1 particle maturation alters the conformation of the Env proteins, a sensitive and quantitative imaging-based Ab-binding assay was used to probe the conformations of full-length and cytoplasmic tail (CT) truncated Env proteins on mature and immature HIV-1 particles. MAb B4e8 binding to immature particles was increased by 15% relative to mature HIV-1 virions and this increase in binding to immature particles was retained on CT-truncated particles. This suggested that exposure of the MAb B4e8 epitope was not markedly altered during HIV-1 maturation. Joyner2011 (binding affinity)
F425-B4e8: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. This MAb is in the list of current MAbs with notable cross-neutralizing activity. Pantophlet2010 (neutralization, variant cross-reactivity, review)
F425-B4e8: This review outlines the general structure of the gp160 viral envelope, the dynamics of viral entry, the evolution of humoral response, the mechanisms of viral escape and the characterization of broadly neutralizing Abs. It is noted that this MAb neutralizes a subset of primary isolates from subtypes B, C and D. Gonzalez2010 (neutralization, variant cross-reactivity, escape, review)
B4e8: Unlike the MPER MAbs tested, B4e8 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions (PSV) by B4e8. However, trimeric JR-FL MC was not captured more efficiently by B4e8 than nontrimeric Envs from JR-CSF MC virus. Leaman2010
F425-B4e8: F425-B4e8 sequence-independent mode of epitope recognition is reviewed in detail. The review also summarizes on how different modes of Ab binding and recognition are used to overcome viral evasion tactics and how this knowledge may be used to re-elicit responses in vivo. Kwong2009a (antibody binding site, review)
B4e8: The crystal structure for VRC01 in complex with an HIV-1 gp120 core from a clade A/E recombinant strain was analyzed to understand the structural basis for its neutralization breadth and potency. The number of mutations from the germline and the number of mutated contact residues for B4e8 were smaller than those for VRC01. Zhou2010 (neutralization, structure)
F425/b4e8: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. F425 neutralization activity was tested for pseudoviruses with the mutations relative to the WT. F425 neutralization was not affected by the three mutations. Unlike PG9 and PG16, F425 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses. Walker2010 (neutralization)
F425: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:3-64*01, IGHD:3-22, D-RF:2, IGHJ:3. There was a preferential usage of the VH5-51 gene segment for V3 Abs. The usage of the VH4 family for the V3 Abs was restricted to only one gene segment, VH4-59, and the VH3 gene family was used at a significantly lower level by these Abs. The V3 Abs preferentially used the JH3 and D2-15 gene segments. Gorny2009 (antibody sequence)
F425 B4e8: Two chimeras were constructed from a new HIV-2KR.X7 proviral scaffold where the V3 region was substituted with the V3 from HIV-1 YU2 and Ccon, generating subtype B and C HIV-2 V3 chimera. Both chimeras were sensitive to neutralization by F425 B4e8, while the wildtype derived viruses HIV-2KR.X4 and HIV-2KR.X7 were completely resistant. A V3 linear peptide from HIV-1 JR-FL was able to absorb a substantial proportion of F425 B4e8 neutralizing activity, while a peptide from HIV-1 YU2 did not remove any of the F425 B4e8 neutralizing activity. Fc-V3 fusion protein from subtype B completely eliminated F425 B4e8-mediated neutralization while a fusion protein from subtype C eliminate only a fraction of neutralizing activity. However, F425 B4e8 was unable to neutralize the primary HIV-1 BORI virus while it neutralized the HIV-2-BORI V3 chimera. Competition assays showed that most of the plasmas derived from subtype B and C chronically infected individuals had neutralizing activity that was V3 specific and dependent upon residued in the V3 crown that overlap 447-52D and F425 B4e8 epitopes. Also, 55 early founder viral Env proteins from 47 subjects acutely infected with subtype B virus were tested for susceptibility to F425 B4e8. 51 viruses were resistant to neutralization by F425 B4e8, but many showed sensitivity to this Ab once conformational changes were induced with sCD4. This indicates that the V3 region in primary HIV-1 Envs is highly conserved but is shielded from Ab recognition. Davis2009 (HIV-2, neutralization, acute/early infection)
F425 B4e8: Two different but genetically related viruses, CC101.19 and D1/85.16, which are resistant to small molecule CCR5 inhibitors, and two clones from their inhibitor sensitive parental strain CC1/85, were used to analyze interactions of HIV-1 with CCR5. CC101.19 had 4 substitutions in the V3 region and D1/85.16 had 3 changes in gp41. F425 B4e8 bound detectably to gp120 of CC101.19 but this was greatly reduced compared to the binding of F425 B4e8 to gp120 of the other three viruses. F425 B4e8 bound equally well to the V3 peptide alone of the four viruses. F425 B4e8 neutralized CC101.19 with equal capacity as the parental virus, and was the only MAb able to neutralize D1/85.16. Berro2009 (neutralization, binding affinity)
F425 B4e8: This report investigated whether mannose removal alters gp120 immunogenicity in mice. Approximately 55 mannose residues were removed from gp120 by mannosidase digestion creating D-gp120 for immunization. F425 B4e8 was able to bind to D-gp120 comparably as to the untreated gp120, indicating that the mannosidase digestion did not affect the antigenicity of gp120. Banerjee2009 (binding affinity)
F425 B4e8: This Ab neutralized infection of PBLs with various HIV-1 strains. However, it did not inhibit transcytosis of cell-free or cell-associated virus across a monolayer of epithelial cells. A mixture of 13 MAbs directed to well-defined epitopes of the HIV-1 envelope, including F425 B4e8, did not inhibit HIV-1 transcytosis, indicating that envelope epitopes involved in neutralization are not involved in mediating HIV-1 transcytosis. When the mixture of 13 MAbs and HIV-1 was incubated with polyclonal anti-human γ chain, the transcytosis was partially inhibited, indicating that agglutination of viral particles at the apical surface of cells may be critical for HIV transcytosis inhibition by HIV-specific Abs. Chomont2008 (neutralization)
F425-B4e8: This review summarizes data on possible vaccine targets for elicitation of neutralizing Abs and discusses whether it is more practical to design a clade-specific than a clade-generic HIV-1 vaccine. Development of a neutralizing Ab response in HIV-1 infected individuals is reviewed, including data that show no apparent division of different HIV-1 subtypes into clade-related neutralization groups. Also, a summary of the neutralizing activity of MAb F425-B4e8 in different HIV-1 clades is provided. McKnight2007 (variant cross-reactivity, review)
F425-B4e8: A mathematical model was developed and used to derive transmitted or founder Env sequences from individuals with acute HIV-1 subtype B infection. All but three of the transmitted or early founder Envs were resistant to neutralization by F425-B4e8, indicating that the coreceptor binding surfaces on transmitted/founder Envs are conformationally masked. sCD4 could trigger a conformational change in gp120 of these Envs and render the virus susceptible to neutralization by F425-B4e8. Keele2008 (neutralization, acute/early infection)
F425: In order to assess whether small molecule CCR5 inhibitor resistant viruses were more sensitive to neutralization by NAbs, two escape mutant viruses, CC101.19 and D1/85.16, were tested for their sensitivity to neutralization by F425, compared to the sensitivity of CC1/85 parental isolate and the CCcon.19 control isolate. The CC101.19 escape mutant has 4 sequence changes in V3 while the D1/85.16 has no sequence changes in V3 and relies on other sequence changes for its resistance. None of the control or resistant viruses were sensitive for neutralization by F425, although F425 bound strongly to gp120 from CC1/85 and CC101.19. These results indicate that V3-dependent and -independent changes responsible for CCR5 inhibitor resistance do not necessarily alter the exposure of V3 to some of the V3 Abs. Pugach2008 (antibody binding site, co-receptor, neutralization, binding affinity)
F425 B4e8: To examine sequence and conformational differences between subtypes B and C, several experiments were performed with 11 MAbs regarding binding and neutralization. Both binding and neutralization studies revealed that the 11 MAbs could be divided in three different groups, and that the most differences between the subtypes were located in the stem and turn regions of V3. F425 B4e8 belonged to the group 1 MAbs, which are able to bind both subtype B and C gp120 proteins and peptides. F425 B4e8 was able to bind both subtype C V3 in the subtype B Env backbone chimera, and reverse, indicating that F425 B4e8 binds to V3 in a way that is not affected by the gp120 backbone. For subtype B, changes in the position 13 (H13R) and/or position 18 (R18Q) showed no difference of F425 B4e8 binding compared to wildtype. For subtype C, H13 residue enhanced binding of F425 B4e8, but the R18 mutation reduced binding, indicating that R18 affects the conformation of V3 subtype C. F425 B4e8 did not neutralize JR-FL isolate, but did neutralize SF162. A chimeric SF162 variant with a JR-FL-like V3 sequence was hypersensitive to neutralization by F425 B4a1, suggesting an important role of one or more of the three V3 amino acids that differ between these two isolates in defining the epitope and/or structure of the protein. Patel2008 (neutralization, variant cross-reactivity, binding affinity, subtype comparisons)
F425: 24 broadly neutralizing plasmas from HIV-1 subtype B and C infected individuals were investigated using a series of mapping methods to identify viral epitopes targeted by NAbs. V3 Ab activity was measured by three assays where F425 was used as a control. Binley2008 (neutralization)
F425-B4e8: Five amino acids in the gp41 N-terminal region that promote gp140 trimerization (I535, Q543, S553, K567 and R588) were considered. Their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells was studied. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. F425-B4e8 captured significantly fewer mutant pseudovirions than wild type, but F425-B4e8 inhibited infection of the two pseudoviruses with comparable potencies. Dey2008 (binding affinity)
F425b4e8: Point mutations in the highly conserved structural motif LLP-2 within the intracytoplasmic tail of gp41 resulted in conformational alternations of both gp41 and gp120. The alternations did not affect virus CD4 binding, coreceptor binding site exposure, or infectivity of the virus, but did result in increased relative neutralization resistance of the LLP-2 mutant virus to F425b4e8, compared with wildtype virus. The increased neutralization resistance of LLP-2 virus was associated with decreased F425b4e8 binding to its epitope. Kalia2005 (antibody binding site, neutralization, binding affinity)
F425b: This Ab recognized gp120 glycoproteins from CCR5-using MN, ADA and YU2 strains and from the dual-tropic 89.6 strain, but it did not recognize the gp120 from the CXCR4-using HXBc2. gp120 from HXBc2 containing the V3 loop of YU2 strain was efficiently recognized by F425b, indicating the role of the V3 loop in recognition of CCR5 strains by this Ab. Changing the residues 325 and 326 at the base of the V3 loop from the amino acids predominant in the CXCR4-using strains to amino acids predominant in the CCR5-using strains did not result in binding of F425b. Xiang2005 (antibody binding site, co-receptor)
F425: This review focuses on the importance of neutralizing Abs in protecting against HIV-1 infection, including mechanisms of Ab interference with the viral lifecycle, Ab responses elicited during natural HIV infection, and use of monoclonal and polyclonal Abs in passive immunization. In addition, vaccine design strategies for eliciting of protective broadly neutralizing Abs are discussed. MAbs included in this review are: 2F5, Clone 3 (CL3), 4E10, Z13, IgG1b12, 2G12, m14, 447-52D, 17b, X5, m16, 47e, 412d, E51, CM51, F105, F425, 19b, 2182, DO142-10, 697-D, 448D, 15e and Cβ1. McCann2005 (neutralization, variant cross-reactivity, review)
F425 B4e8: This Ab was shown to inhibit HIV-1 BaL replication in both macrophages and PHA-stimulated PBMCs. It is suggested that inhibition of HIV replication by this Ab for macrophages and iDCs can occur by two distinct mechanisms, neutralization of infectivity involving only the Fab part of the IgG, and, an IgG-FcγR-dependent interaction leading to endocytosis and degradation of HIV particles. Holl2006 (dendritic cells)
F425 B4e8: The neutralization breadth of F425 B4e8 was assessed using a panel of 40 primary HIV-1 isolates. The Ab neutralized 8/16 clade B, 1/11 clade C and 2/6 clade D viruses, and its neutralization activity was comparable to MAb 447-52D. In contrast to previous reports, it is suggested here that F425 B4e8 interacts primarily with the crown/tip of V3, based on the scanning mutagenesis analyses of the V3 region, in particular with Ile309, Arg315, and Phe317. Pantophlet2007 (antibody binding site, neutralization, variant cross-reactivity, subtype comparisons)
F425 B4e8: Peptides containing the V3 epitope for F425 B4e8 did not inhibit neutralization by broadly neutralizing sera from two clade B and one clade A infected asymptomatic individuals. Dhillon2007 (antibody binding site, neutralization, variant cross-reactivity)
F425 B4e8: Antigens were designed to attempt to target immune responses toward the IgG1b12 epitope, while minimizing antibody responses to less desirable epitopes. One construct had a series of substitutions near the CD4 binding site (GDMR), the other had 7 additional glycans (mCHO). The 2 constructs did not elicit b12-like neutralizing antibodies, but both antigens successfully dampened other responses that were intended to be dampened while not obscuring b12 binding. V3 MAbs (447-52D, 19b, F245-B4e8 and 39F) bound to the GDMR antigen, but either did not bind or had diminished binding to mCHO. Selvarajah2005 (vaccine antigen design, vaccine-induced immune responses)
F425 B4e8: By adding N-linked glycosylation sites to gp120, epitope masking of non-neutralizing epitopes can be achieved leaving the IgG1b12 binding site intact. This concept was originally tested with the addition of four glycosylation sites, but binding to b12 was reduced. It was modified here to exclude the C1 N-terminal region, and to include only three additional glycosylation sites. This modified protein retains full b12 binding affinity and it masks other potentially competing epitopes, and does not bind to 21 other MAbs to 7 epitopes on gp120, including F425 B4e8. This MAb bound to the initial construct, but introduction of glycosylation sites at positions 320 and 325 inhibited binding. Pantophlet2004

References

Showing 39 of 39 references.

Isolation Paper
Cavacini2003 Lisa Cavacini, Mark Duval, Leslie Song, Rebecca Sangster, Shi-hua Xiang, Joseph Sodroski, and Marshall Posner. Conformational Changes in env Oligomer Induced by an Antibody Dependent on the V3 Loop Base. AIDS, 17(5):685-689, 28 Mar 2003. PubMed ID: 12646791. Show all entries for this paper.

Chomont2008 Nicolas Chomont, Hakim Hocini, Jean-Chrysostome Gody, Hicham Bouhlal, Pierre Becquart, Corinne Krief-Bouillet, Michel Kazatchkine, and Laurent Bélec. Neutralizing Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Do Not Inhibit Viral Transcytosis Through Mucosal Epithelial Cells. Virology, 370(2):246-254, 20 Jan 2008. PubMed ID: 17920650. Show all entries for this paper.

Joyner2011 Amanda S. Joyner, Jordan R. Willis, James E.. Crowe, Jr., and Christopher Aiken. Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles. PLoS Pathog., 7(9):e1002234, Sep 2011. PubMed ID: 21931551. Show all entries for this paper.

Kalia2005 Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412. Show all entries for this paper.

Lara2011 Humberto H. Lara, Liliana Ixtepan-Turrent, Elsa N. Garza Treviño, and Dinesh K. Singh. Use of Silver Nanoparticles Increased Inhibition of Cell-Associated HIV-1 Infection by Neutralizing Antibodies Developed against HIV-1 Envelope Proteins. J. Nanobiotechnology, 9:38, 2011. PubMed ID: 21923937. Show all entries for this paper.

Pantophlet2010 Ralph Pantophlet. Antibody Epitope Exposure and Neutralization of HIV-1. Curr. Pharm. Des., 16(33):3729-3743, 2010. PubMed ID: 21128886. Show all entries for this paper.

Tudor2012 Daniela Tudor, Huifeng Yu, Julien Maupetit, Anne-Sophie Drillet, Tahar Bouceba, Isabelle Schwartz-Cornil, Lucia Lopalco, Pierre Tuffery, and Morgane Bomsel. Isotype Modulates Epitope Specificity, Affinity, and Antiviral Activities of Anti-HIV-1 Human Broadly Neutralizing 2F5 Antibody. Proc. Natl. Acad. Sci. U.S.A., 109(31):12680-12685, 31 Jul 2012. PubMed ID: 22723360. Show all entries for this paper.

Liu2003 Fangbing Liu, Pablo Lopez Bergami, Mark Duval, David Kuhrt, Marshall Posner, and Lisa Cavacini. Expression and Functional Activity of Isotype and Subclass Switched Human Monoclonal Antibody Reactive with the Base of the V3 Loop of HIV-1 gp120. AIDS Res. Hum. Retroviruses, 19(7):597-607, Jul 2003. PubMed ID: 12908937. Show all entries for this paper.

Bell2008 Christian H. Bell, Ralph Pantophlet, André Schiefner, Lisa A. Cavacini, Robyn L. Stanfield, Dennis R. Burton, and Ian A. Wilson. Structure of Antibody F425-B4e8 in Complex with a V3 Peptide Reveals a New Binding Mode for HIV-1 Neutralization. J. Mol. Biol., 375(4):969-978, 25 Jan 2008. PubMed ID: 18068724. Show all entries for this paper.

Ahmed2012 Fatima K. Ahmed, Brenda E. Clark, Dennis R. Burton, and Ralph Pantophlet. An Engineered Mutant of HIV-1 gp120 Formulated with Adjuvant Quil A Promotes Elicitation of Antibody Responses Overlapping the CD4-Binding Site. Vaccine, 30(5):922-930, 20 Jan 2012. PubMed ID: 22142583. Show all entries for this paper.

Gach2013 Johannes S. Gach, Heribert Quendler, Tommy Tong, Kristin M. Narayan, Sean X. Du, Robert G. Whalen, James M. Binley, Donald N. Forthal, Pascal Poignard, and Michael B. Zwick. A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1. PLoS One, 8(8):e72054, 2013. PubMed ID: 23991039. Show all entries for this paper.