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Displaying record number 1421

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• 2909: The authors note that 2909 is a strain-specific mAb for the heterologous strain SF162 and targets an epitope in V2. The limited neutralization breadth of 2909 could be explained by the requirement for a lysine at position 160 (normally glycosylated) creating a hole in the Env glycan shield. Wibmer2016 (antibody binding site)
• 2909: The authors note that 2909 can only neutralize viruses that lack a glycan at the N160 position. Antibody 2909 was used as a control in neutralization assays for comparison with other V2 apex nAbs. Andrabi2015 (neutralization)
• 2909: This is a conference poster abstract identified human and rhesus MAbs recognizing distinct groups of epitopes that elicit neutralizing Abs against autologous HIV-1 strains. Four HMAbs and nine RhMAbs identified three groups of autologous neutralization epitopes. Robinson2008 (autologous responses, neutralization)
• 2909: Antigenic properties of 2 biochemically stable and homogeneous gp140 trimers (A clade 92UG037 and C clade CZA97012) were compared with the corresponding gp120 monomers derived from the same percursor sequences. The trimers had nearly all the antigenic properties expected for native viral spikes and were markedly different from monomeric gp120. 2909 has been discussed as NAb recognizing trimer-specific, glycan-dependent quaternary epitope. Kovacs2012 (antibody binding site, neutralization, binding affinity)
• 2909: The study used the swarm of quasispecies representing Env protein variants to identify mutants conferring sensitivity and resistance to BnAbs. Libraries of Env proteins were cloned and in vitro mutagenesis was used to identify the specific AA responsible for altered neutralization/resistance, which appeared to be associated with conformational changes and exposed epitopes in different regions of gp160. The result showed that sequences in gp41, the CD4bs, and V2 domain act as global regulator of neutralization sensitivity. ORourke2012 (neutralization)
• M2909: CAP256, an HIV-1 subtype C-infected (and subsequently superinfected) participant enrolled in the CAPRISA Acute Infection cohort was studied. CAP256 binds to quaternary neutralizing epitopes (QNE). MAb 2909 was referred as the first to exhibit binding to QNEs. Moore2011
• 2909: The rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1 is discussed in relation to understanding of vaccine recognition sites, the structural basis of interaction with HIV-1 env and vaccine developmental pathways. 2909 has been discussed regarding the sites of HIV-1 vulnerability to neutralizing antibodies. Kwong2011 (antibody binding site, neutralization, vaccine antigen design, review)
• 2909: The crystal structures of the Fabs of human MAb 2909 and macaque MAb 2.5B were determined. The structures were highly similar and had long, extended CDR H3 regions with a straight beta hairpin structure and with shallow binding pockets formed by the base region of CDRH3 and other CDRs. The Optimal Docking Area (ODA) method was applied for analysis. The hotspots for protein-protein interactions were concentrated on CDR H3s, suggesting that the apexes of the CDR H3 regions in both MAbs are likely to play central roles in epitope interactions. Figure 3 lists possible antigen binding pockets of these Fabs, identified by computational analysis. Spurrier2011 (structure)
• 2909: The study showed that alteration between a rare lysine K and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. These neutralization profiles were mutually exclusive (160K for MAb 2909, 160N for PG16/PG9); there was no case of a virus that was sensitive to both 2909 and PG16/PG9 neutralization. Several more positions were studied: both the PG and 2909 MAbs do not require an asparagine at position 156 for neutralization, both the PG and 2909 antibodies tolerate amino acid variation at position 165, and neither the PG nor the 2909 MAb could tolerate a glutamic acid at position 168. Wu2011a (antibody binding site, escape)
• 2909: Crystal structure of the antigen-binding fragment (Fab) of 2909 at a 3.3-Å resolution was determined and compared to the previously determined structure of PG16. The 2909 structure was dominated by a heavy-chain third-complementarity-determining region (CDR H3) of 21 residues, which comprised 36% of the combining surface and formed a β-hairpin club extending ∼20 Å beyond the rest of the antibody. Comparison of 2909 to PG16 showed that both utilize protruding, anionic CDR H3s for recognition. Both 2909 and PG16 are highly dependent on the residue at position 160 in the V2 loop and the primary reason 2909 does not neutralize as broadly as PG16 was suggested to relate specifically to the N160K substitution, thereby suggesting that 2909 and PG16 recognize different immunotypes of the same epitope. Changela2011 (antibody binding site, structure)
• 2909: MAbs PG9, PG16, CH04, PGT145 and 2909 showed anionic protruding CDR H3s, most of which were tyrosine sulphated. All also displayed β-hairpins and, although these varied substantially in orientation relative to the rest of the combining site, all appeared capable of penetrating an N-linked glycan shield to reach a cationic protein surface. McLellan2011 (structure)
• 2909: This review discusses current understanding of Env neutralization by antibodies in relation to epitope exposure and how this insight might benefit vaccine design strategies. 2909 was mentioned as the first identified oligomer-specific MAb. MAb 2909 involves mainly the V2 and V3 regions, with specificity governed largely by type-specific residues in V2, and as a consequence of this binding requirement, 2909 only neutralizes SF162, a neutralization-sensitive virus. Pantophlet2010 (neutralization, variant cross-reactivity, review)
• 2909: Unlike the MPER MAbs tested, 2909 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. Leaman2010
• 2909: This human Ab was compared to the Abs derived from B-cell cultures from SHIV-infected rhesus macaques and human MAbs 447, 3.9F, IgGb12, 830A and sCD4. 2909 showed potent neutralizing activity against the homologous virus (SF162). 2909 captured SF162 and SF162ΔV1, but did not capture ΔV2 or ΔV3 virions, indicating that the V2 and V3 loops are involved in forming the quaternary epitope of this Ab. 2909 was then compared to macaque MAbs 2.2G, 2.3E, 2.5B. MAb 2909 blocked the capture of virions by MAbs 2.2G, 2.3E, 2.5B and partially blocked it by the human MAb 447. 2909 capture of virions was blocked by MAbs 447 and partially blocked by 830A and sCD4. Amino acid K at position 158 was critical for 2909 binding and neutralization. N-linked glycosylation at position 154 and 186 were not necessary for binding and neutralization by 2909. However, elimination of the N-linked glycosylation at position 195 significantly abrogated 2909 neutralizing activity, suggesting that the sugars at this position may be a part of the 2909 epitope. Robinson2010 (antibody binding site, glycosylation, neutralization, binding affinity)
• 2909: 2909 two-component 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)
• 2909: 2909 bound to SF162 wild type virions and transfected cells but did not bind to SF162 mutant carrying only the monomeric form of the Env protein, indicating that 2909 epitope is present only on the Env trimer. 2909 exhibited lower binding activity to SF162 wild type compared to 447-52D, suggesting that 2909 epitope may not be formed on each trimer. Kimura2009 (antibody binding site, binding affinity)
• 2909: Novel methods for generation of broadly neutralizing Abs, such as PG9 and PG16 are reviewed. This review also summarizes PG9 and PG16 MAbs, and their similarity to 2909 MAb. Kwong2009 (review)
• 2909: Broadly neutralizing sera from elite neutralizers exhibited significant sensitivities to mutations I165A, N332A, and N160K. 2909 neutralization activity was tested for pseudoviruses with the mutations relative to the WT. 2909 was shown to require I165A for potent neutralizing activity. Unlike PG9 and PG16, 2909 neutralized kifunensine-treated pseudoviruses with similar potency as wild type pseudoviruses. Walker2010 (neutralization)
• 2909: The neutralizing activity of V1 and V2 Abs, such as MAb 2909, is reviewed. Pantophlet2006 (antibody binding site, neutralization)
• 2909: Replacing V3 domain of SF162, which is neutralized by 2909, with V3 from different HIV-1 clades resulted in significant reductions in sensitivity to neutralization by this antibody. However, the only variant totally resistant was CRF01_AE. The main requirement for reactivity of 2909 in V2 was a rare polymorphism at position 160 or 161, and to a lesser extent at positions 167 and 169. It was also found that the neutralization sensitive SF162 variant actually expressed a suboptimal form of 2909 epitope where a mutation N167D resulted in more robust neutralization. Position 167 in V2 dictates the specificities of three type-specific neutralizing MAbs that bind to an otherwise relatively conserved epitope in involving V2: 2909, C108g, and 10/76b. Honnen2007 (antibody binding site, variant cross-reactivity)
• 2909: 2909 is a NAb that was produced by fusion of heteromyeloma SHM-D33 with Epstein-Barr virus transformed PBMC and selection by a neutralization assay. The PBMC were derived from an HIV-1 infected individual who maintained a low viral load after 15 years of infection with no therapy. The MAb very potently neutralizes SF162, but has a narrow range of activity, and did not neutralize autologous virus, nor primary isolates from clade A (VI191, CA1, and 92RW021),clades B (BX08, CA5, and BaL), clade C (95ZW2036) and clade F (CA20 and 93BR029). Sequence analysis of the variable domain of the heavy chain of 2909 shows that it is comprised of IgHV3-43, IgHJ6, and IgHD5-12. 2909 recognizes a quartenary structure present on intact SF162 virions and does not bind to soluble or recombinant Envelope proteins. 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 (anti-C5), 1418 (irrelevant control MAb), nor 2G12 (anti-carbohydrate); in fact, 2G12 enhanced 2909 binding. Gorny2005 (antibody generation, variant cross-reactivity, subtype comparisons, antibody sequence)

References

Showing 21 of 21 references.

Isolation 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.

Andrabi2015 Raiees Andrabi, James E. Voss, Chi-Hui Liang, Bryan Briney, Laura E. McCoy, Chung-Yi Wu, Chi-Huey Wong, Pascal Poignard, and Dennis R. Burton. Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design. Immunity, 43(5):959-973, 17 Nov 2015. PubMed ID: 26588781. Show all entries for this paper.

Changela2011 Anita Changela, Xueling Wu, Yongping Yang, Baoshan Zhang, Jiang Zhu, Glenn A. Nardone, Sijy O'Dell, Marie Pancera, Miroslaw K. Gorny, Sanjay Phogat, James E. Robinson, Leonidas Stamatatos, Susan Zolla-Pazner, John R. Mascola, and Peter D. Kwong. Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1. J. Virol., 85(6):2524-2535, Mar 2011. PubMed ID: 21191009. Show all entries for this paper.

Honnen2007 W. J. Honnen, C. Krachmarov, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and A. Pinter. Type-Specific Epitopes Targeted by Monoclonal Antibodies with Exceptionally Potent Neutralizing Activities for Selected Strains of Human Immunodeficiency Virus Type 1 Map to a Common Region of the V2 Domain of gp120 and Differ Only at Single Positions from the Clade B Consensus Sequence. J. Virol., 81(3):1424-1432, Feb 2007. PubMed ID: 17121806. 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.

Kovacs2012 James M. Kovacs, Joseph P. Nkolola, Hanqin Peng, Ann Cheung, James Perry, Caroline A. Miller, Michael S. Seaman, Dan H. Barouch, and Bing Chen. HIV-1 Envelope Trimer Elicits More Potent Neutralizing Antibody Responses than Monomeric gp120. Proc. Natl. Acad. Sci. U.S.A., 109(30):12111-12116, 24 Jul 2012. PubMed ID: 22773820. Show all entries for this paper.

Kwong2009 Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Mining the B Cell Repertoire for Broadly Neutralizing Monoclonal Antibodies to HIV-1. Cell Host Microbe, 6(4):292-294, 22 Oct 2009. PubMed ID: 19837366. 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.

Kwong2011 Peter D. Kwong, John R. Mascola, and Gary J. Nabel. Rational Design of Vaccines to Elicit Broadly Neutralizing Antibodies to HIV-1. Cold Spring Harb. Perspect. Med., 1(1):a007278, Sep 2011. PubMed ID: 22229123. 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.

McLellan2011 Jason S. McLellan, Marie Pancera, Chris Carrico, Jason Gorman, Jean-Philippe Julien, Reza Khayat, Robert Louder, Robert Pejchal, Mallika Sastry, Kaifan Dai, Sijy O'Dell, Nikita Patel, Syed Shahzad-ul-Hussan, Yongping Yang, Baoshan Zhang, Tongqing Zhou, Jiang Zhu, Jeffrey C. Boyington, Gwo-Yu Chuang, Devan Diwanji, Ivelin Georgiev, Young Do Kwon, Doyung Lee, Mark K. Louder, Stephanie Moquin, Stephen D. Schmidt, Zhi-Yong Yang, Mattia Bonsignori, John A. Crump, Saidi H. Kapiga, Noel E. Sam, Barton F. Haynes, Dennis R. Burton, Wayne C. Koff, Laura M. Walker, Sanjay Phogat, Richard Wyatt, Jared Orwenyo, Lai-Xi Wang, James Arthos, Carole A. Bewley, John R. Mascola, Gary J. Nabel, William R. Schief, Andrew B. Ward, Ian A. Wilson, and Peter D. Kwong. Structure of HIV-1 gp120 V1/V2 Domain with Broadly Neutralizing Antibody PG9. Nature, 480(7377):336-343, 15 Dec 2011. PubMed ID: 22113616. Show all entries for this paper.

Moore2011 Penny L. Moore, Elin S. Gray, Daniel Sheward, Maphuti Madiga, Nthabeleng Ranchobe, Zhong Lai, William J. Honnen, Molati Nonyane, Nancy Tumba, Tandile Hermanus, Sengeziwe Sibeko, Koleka Mlisana, Salim S. Abdool Karim, Carolyn Williamson, Abraham Pinter, Lynn Morris, and CAPRISA 002 Study. Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 loop. J. Virol., 85(7):3128-3141, Apr 2011. PubMed ID: 21270156. Show all entries for this paper.

ORourke2012 Sara M. O'Rourke, Becky Schweighardt, Pham Phung, Kathryn A. Mesa, Aaron L. Vollrath, Gwen P. Tatsuno, Briana To, Faruk Sinangil, Kay Limoli, Terri Wrin, and Phillip W. Berman. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies. J. Virol., 86(22):12105-12114, Nov 2012. PubMed ID: 22933284. 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.

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.

Robinson2008 J.E. Robinson, K. Franco, D. Elliott, C. Derdeyn, D. Montefiori, H. Tang, M. Gorny, S. Zolla-Pazner, Z. Kraft, and L. Stamatatos. Human and Rhesus MAbs Recognizing Distinct Groups of Epitopes that Elicit Neutralizing Antibodies against Autologous HIV-1 Strains. AIDS Res. Hum. Retroviruses, 24(s1):48, October 2008. 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.

Spurrier2011 Brett Spurrier, Jared M. Sampson, Maxim Totrov, Huiguang Li, Timothy O'Neal, Constance Williams, James Robinson, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Structural Analysis of Human and Macaque mAbs 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120. Structure, 19(5):691-699, 11 May 2011. PubMed ID: 21565703. 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.

Wibmer2016 Constantinos Kurt Wibmer, Jason Gorman, Colin S. Anthony, Nonhlanhla N. Mkhize, Aliaksandr Druz, Talita York, Stephen D. Schmidt, Phillip Labuschagne, Mark K. Louder, Robert T. Bailer, Salim S. Abdool Karim, John R. Mascola, Carolyn Williamson, Penny L. Moore, Peter D. Kwong, and Lynn Morris. Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site. J. Virol., 90(22):10220-10235, 15 Nov 2016. PubMed ID: 27581986. Show all entries for this paper.

Wu2011a Xueling Wu, Anita Changela, Sijy O'Dell, Stephen D. Schmidt, Marie Pancera, Yongping Yang, Baoshan Zhang, Miroslaw K. Gorny, Sanjay Phogat, James E. Robinson, Leonidas Stamatatos, Susan Zolla-Pazner, Peter D. Kwong, and John R. Mascola. Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies. J. Virol., 85(9):4578-4585, May 2011. PubMed ID: 21325411. Show all entries for this paper.

Displaying record number 2481

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Notes

Showing 2 of 2 notes.

• 2.5B: The crystal structures of the Fabs of human MAb 2909 and macaque MAb 2.5B were determined. The structures were highly similar and had long, extended CDR H3 regions with a straight beta hairpin structure and with shallow binding pockets formed by the base region of CDRH3 and other CDRs. The Optimal Docking Area (ODA) method was applied for analysis. The hotspots for protein-protein interactions were concentrated on CDR H3s, suggesting that the apexes of the CDR H3 regions in both MAbs are likely to play central roles in epitope interactions. Figure 3 lists possible antigen binding pockets of these Fabs, identified by computational analysis. Spurrier2011 (structure)
• 2.5B: This Ab was derived from B-cell cultures from SHIV-infected rhesus macaques. 2.5B showed potent neutralizing activity against the homologous virus (SF162) but not heterologous viruses. 2.5B showed no reactivity with recombinant soluble SF162 or gp140 constructs, indicating that this Ab recognizes a quaternary structure on intact virions. 2.5B captured SF162 and SF162ΔV1, but did not capture ΔV2 or ΔV3 virions, indicating that the V2 and V3 loops are involved in forming the quaternary epitope of this Ab. 2.5B capture of virions was blocked by MAbs 447 and 2909, and partially blocked by 830A and sCD4. Amino acid K at position 158 was not critical for 2.5B binding and the presence of sugars at this position blocked binding of 2.5B. N-linked glycosylations at positions 154 and 186 were not necessary for binding and neutralization by 2.5B. However, elimination of the N-linked glycosylation at position 195 significantly reduced 2.5B neutralizing activity. Robinson2010 (antibody binding site, antibody generation, glycosylation, neutralization, binding affinity)

References

Showing 2 of 2 references.

Isolation 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.

Spurrier2011 Brett Spurrier, Jared M. Sampson, Maxim Totrov, Huiguang Li, Timothy O'Neal, Constance Williams, James Robinson, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Structural Analysis of Human and Macaque mAbs 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120. Structure, 19(5):691-699, 11 May 2011. PubMed ID: 21565703. Show all entries for this paper.