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Displaying record number 3481
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3BNC117/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-CD4bs/anti-fusion peptide combination, 3BNC117/PGT151, against a 7-cross-clade panel of tier 2/3 showed it exhibited equal activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3515
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PGT151/10-1074: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-V3 interface combination, PGT151/10-1074, against a 7-cross-clade panel of tier 2/3 showed it exhibited synergistic activity compared to its respective parental counterparts. Using a multi-clade virus panel of 119 strains, the PGT151/10-1074 bispecific is more potent than either parental antibody, and equal to a predicted mix of parental antibodies.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3518
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PGT151/35O22: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-gp120-gp41 interface combination, PGT151/35O22 was not tested as an IgG3 hinge variant bispecific. Using a multi-clade virus panel, the PGT151/35O22 IgG1-hinge bispecific is equal to a predicted mix of parental antibodies.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3525
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8ANC195/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-gp41-120 interface/anti-fusion peptide, 8ANC195/PGT151, against a 7-cross-clade panel of tier 2/3 showed it exhibited synergistic activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3533
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PGT151/10-1074: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. On a panel of 208 pseudoviruses, the IgG3C hinge variant of PGT151/10-1074 exhibited a similar degree of neutralization compared to the original IgG1 version.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3542
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PGT151-IgG3C-: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. In general, PGT151-IgG3C- neutralized slightly better than PGT151-IgG1 (Fig.S2).
Bournazos2016
(antibody generation, neutralization)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3675
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8ANC131/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-CD4bs/anti-fusion peptide combination, 8ANC131/PGT151, showed it had mildly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3681
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CH103/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-CD4bs/anti-fusion peptide combination, CH103/PGT151, showed it had mildly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3695
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PGT121/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-V3/anti-fusion peptide, PGT121/PGT151, showed it had strong synergistic activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3699
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PGT128/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-V3/anti-fusion peptide combination, PGT128/PGT151, showed it had synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3704
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PGT135/PGT151: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-V3/anti-fusion peptide combination, PGT128/PGT151, showed it had strongly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3707
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PGT151/10E8: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-MPER combination, PGT151/10E8, showed it had strongly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3708
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PGT151/3BC176: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-CD4bs combination, PGT151/3BC176, showed it had about equal neutralization activity as its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3709
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PGT151/PGDM1400: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-V2glycan apex combination, PGT151/PGDM1400, showed it had mildly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3710
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PGT151/PGT145: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-V2glycan apex combination, PGT151/PGT145, showed it had strongly synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3711
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PGT151/PG16: biNAbs (bispecific anti-Env neutralizing antibodies) with potent activity were constructed using an engineered IgG3 hinge domain to increase Fab flexibility necessary for hetero-bivalent binding to HIV-1 Env trimer since biNAbs with IgG1 hinges exhibited reduced neutralization potency compared to their parental bNAbs. While neutralization was generally improved, some combinations of bNAbs were synergistic in potency. Analysis of the neutralization activity of anti-fusion peptide/anti-V2glycan apex combination, PGT151/PG16, showed it had synergistic neutralization activity compared to its respective parental counterparts.
Bournazos2016
(antibody generation, neutralization, bispecific/trispecific)
References
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Isolation Paper
Bournazos2016
Stylianos Bournazos, Anna Gazumyan, Michael S. Seaman, Michel C. Nussenzweig, and Jeffrey V. Ravetch. Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency. Cell, 165(7):1609-1620, 16 Jun 2016. PubMed ID: 27315478.
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Displaying record number 3107
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MAb ID |
PGT151 (PGT-151) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
gp120-gp41 interface |
Epitope |
(Discontinuous epitope)
|
Subtype |
C |
Ab Type |
fusion peptide // near gp41-gp120 interface |
Neutralizing |
P (tier 2) View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human(IgG) |
Patient |
Donor 31 |
Immunogen |
HIV-1 infection |
Country |
United States |
Keywords |
anti-idiotype, antibody binding site, antibody generation, antibody interactions, antibody lineage, antibody sequence, assay or method development, autologous responses, binding affinity, broad neutralizer, CD4+ CTL, class I down-regulation by Nef, co-receptor, computational prediction, contact residues, effector function, escape, glycosylation, immunotherapy, mutation acquisition, neutralization, polyclonal antibodies, responses in children, review, SIV, structure, subtype comparisons, vaccine antigen design, vaccine-induced immune responses |
Notes
Showing 63 of
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PGT151: This review on antibody mediated cellular cytotoxicity (ADCC) effector functions of anti-HIV-1 antibodies discusses the association between the conformational state of HIV antigen, Env, and binding of either bnAbs or nnAbs (non-neutralizing antibodies) to it and their consequent Fc-mediated ADCC. While bnAbs tend to recognize the 'closed' trimeric State 1 conformation of Env, nnAbs and HIV+ sera bind States 2 and 3 of Env brought to its open conformation by interaction with the host CD4 molecule. Nef/Vpu-induced down regulation of membrane-bound CD4 (and also HLA, Env, BST-2, and NKG2DL) in HIV-infected cells therefore keeps Env in State 1 and these cells, reminiscent of the HIV latent reservoir, are susceptible to bnAb neutralization as well as ADCC. The use of CD4 mimetics (CD4mc), however, can mimic the interaction of CD4 with Env and bring it to its open, nnAb-binding state, after successive exposure of conserved epitopes in the coreceptor binding site (CoRBS) and anti cluster A to nnAbs. Therefore different ADCC-measuring assays are discussed with particular reference to the target cell being either HIV-infected and conducive to bnAb measurements or Env gp120 coated and a measure of nnAb ADCC. The inaccuracies introduced by bystander un-infected cells exposed to shed gp120 are also discussed. Antibodies A32, C11, N5i5 and 2.2c bind to the CD4-induced cluster A epitope on Env. While bnAbs VRC01, 3BNC117, PGT151, 8ANC195, PG9, PG16, PGT121, PGT126 have different binding regions all on closed State 1 of Env and elicit ADCC, the MPER set of 10E8, 4E10 and 2F5 recognize State 1 but do not result in potent ADCC. Studies have shown that some CD4BS bnAbs like b12 protect macaques from SHIV challenge, and 3BNC117 control HIV replication in humanized mice.
Richard2018
(CD4+ CTL, class I down-regulation by Nef, co-receptor, effector function, review)
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PGT151: Eighty clusters of overlapping epitopes that could bind to MHC Class II HLA-DR1*01:01 (DR1) allele were identified by LC-MS/MS using a cell-free processing system that incorporated soluble DR1, HLA-DM (DM), cathepsins, and full-length protein antigens (Gag, Pol, Env, Vif, Tat, Rev, and Nef). Sixteen of Env CD4+ T cell epitopes identified in this study, which were primarily located in the vicinity of the gp120/gp41 interface or the CD4bs, were assessed for overlap with bnAb binding footprints. 2/16 overlapped with the binding footprint of gp120/41 interface-targeting bnAb PGT151: KDA 45-67 (KDAETTLFCASDAKAYETEKHN) and SEL481-499 (SELYKYKVVKIEPLGVAPT). The former was identified only in an unglycosylated form, while the latter was identified as both glycosylated and unglycosylated forms.
Sengupta2023
(antibody binding site)
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PGT151: This preview summarizes the findings of Doud2017, Dingens2017, and Dingens2019 where all possible point mutation escapes from binding nAbs were mapped using a screen of single amino acid changes of soluble Env ectodomain that were then grown and exposed to bnAbs. A loss of interaction/binding to the bnAb suggested neutralization resistant Env and these were deep sequenced, giving an atlas of escape pathways the virus might take. Escape mutants were found to mostly overlap with the 5 structural epitopes (antigen binding regions) of Env even though many of them are not reported in nature. Two additional sets of mutations were found in (1) contact residues that do not affect neutralization and (2) residues outside the 5 structural epitopes. These studies will provide a third characteristic to add to successful bnAb generation besides breadth and potency - "non-susceptibility to escape". PGT151 was the first bnAb studied to map viral escape to it, Doud2017.
Ward2019
(review)
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PGT151: The study describes the generation, crystal structure, and immunogenic properties of a native-like Env SOSIP trimer based on a group M consensus (ConM) sequence. A crystal structure of ConM SOSIP.v7 trimer together with nAbs PGT124 and 35O22 revealed that ConM SOSIP.v7 is structurally similar to other Env trimers. In rabbits, the ConM SOSIP trimer induced serum nAbs that neutralized the autologous Tier 1A virus (ConM from 2004) and a related Tier 1B ConS virus (ConM from 2001). These responses target the trimer apex and were enhanced when the trimers were presented on ferritin nanoparticles. The neutralization of ConM and ConS pseudoviruses was tested against a large panel of nAbs and non-nAbs (2219, 2557, 3074, 3869, 447-52D, 830A, 654-30D, 1008-30D, 1570D, 729-30D, F105, 181D, 246D, 50-69D, sCD4, VRC01, 3BNC117, CH31, PG9, PG16, CH01, PGDM1400, PGT128, PGT121, 10-1074, PGT151, VRC43.01, 2G12, DH511.2_K3, 10E8, 2F5, 4E10); most nAbs were able to neutralize these pseudoviruses. Soluble ConM trimers were able to weakly activate B cells expressing PGT121 and PG16 BCRs but were inactive against those expressing VRC01 and PGT145. In contrast, at the same molar amount of trimers, the ConM SOSIP.v7-ferritin nanoparticles activated all 4 B cells efficiently. Binding of bnAbs 2G12 and PGT145 and non-nAbs F105 and 19b to ConM SOSIP.v7 trimer and SOSIP showed that the ferritin-bound trimer bound more avidly than the soluble trimer. This study shows that native-like HIV-1 Env trimers can be generated from consensus sequences, and such immunogens might be suitable vaccine components to prime and/or boost desirable nAb responses.
Sliepen2019
(neutralization, vaccine antigen design)
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PGT151: Membrane-bound mRNA-encoded BG505-based Apex GT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. All assessed ApexGT constructs, as well as BG505 SOSIP.MD39 (background for Apex constructs), in soluble or membrane-bound forms (encoded by DNA or RNA), had generally similar antigenic profiles and bound mAb PGT151 at high levels.
Willis2022
(antibody binding site)
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PGT151: Following the VRC018 clinical trial of the BG505 DS-SOSIP immunogen, donor N751 showed the highest BG505-reactive ELISA responses. B cells from this donor were sorted for binding to a novel BG505 trimer construct (BG505 glycan base); 8 clones were identified that bound to glycan-base BG505, and 2 were selected for characterization (2C06 and 2C09). The epitopes of 2C06.01 and 2C09.01 were similar to each other, and have substantial overlap with the epitope of VRC34.01, and lower overlap with two other FP-targeting mAbs, PGT151 and ACS202. Binding of mAbs to BG505 DS-SOSIP was compared with binding to the glycan base construct; some mAbs bound to both BG505 DS-SOSIP and glycan base (PGT145, VRC26.25, VRC01, PGT151, VRC34.01, and 2G12), some bound to neither (PG05, 447-52D, and 2557), and 4 base-binding mAbs bound to BG505 DS-SOSIP, but not to BG505 glycan base (1E6, 5H3, 3H2, and 9B9). Structural comparisons were made with X-ray structures of several other fusion peptide mAbs (VRC34.01, ACS202, PGT151, 0PV-a.01, 0PV-b.01, DF1W-a.01, DFPH-a.01, A12V163-a.01, A12V163-b.01, and vFP16.02).
Wang2023
(antibody binding site, binding affinity, structure)
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PGT151:This study identified a B cell lineage of bNAbs in an HIV-1 elite post-treatment controller (ePTC; donor: PTC-005002). Circulating viruses in PTC escaped bNAb pressure but remained sensitive to autologous neutralization by other Ab populations. PGT151 was used as a reference antibody for epitope mapping and binding profile of EPTC112.
Molinos-Albert2023
(binding affinity)
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PGT151: This study explored the basis of the neutralization resistance of tier 3 virus 253-11 (subtype CRF02_AG). Virus 253-11 was resistant to neutralization by 17b, b12, VRC03, F105, SCD4, CH12, Z13e1, PG16, PGT145, 2G12, PGT121, PGT126, PGT128, PGT130, 39F, F240, and 35O22; the virus was sensitive to 3BNC117, NIH45-46G54W, VRC01, 10E8, 2F5, 4E10, PG9, VRC26.26, 10-1074, and PGT151. Virus 253-11 was strikingly resistant to most tested antibodies that target V3/glycans, despite possessing key potential N-linked glycosylation sites, especially N301 and N332, needed for the recognition of this class of antibodies. The resistance of 253-11 was not associated with an unusually long V1/V2 loop, nor with polymorphisms in the V3 loop and N-linked glycosylation sites. The 253-11 MPER was rarely recognized by sera, but was more often recognized in a chimera consisting of a HIV-2 backbone with the 253-11 MPER, suggesting steric or kinetic hindrance of the MPER. Mutations in the 253-11 MPER previously reported to increase the lifetime of the prefusion Env conformation (Y681H, L669S), decreased the resistance of 253-11 to several mAbs, presumably destabilizing its otherwise stable, closed trimer structure. A crystal structure of a recombinant 253-11 SOSIP trimer revealed that the heptad repeat helices in gp41 are drawn in close proximity to the trimer axis and that gp120 protomers also showed a relatively compact form around the trimer axis.
Moyo2018
(neutralization, structure)
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PGT151: This study assessed the ability of single bNAbs and triple bNAb combinations to mediate polyfunctional antiviral activity against a panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies in nonhuman primate models. Most bnAbs assayed were capable of mediating both neutralizing and nonneutralizing effector functions (ADCC and ADCP) against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs was highly strain dependent. Several triple bNAb combinations were identified comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. In assays using the transmitted/founder SHIV.C.CH505, there was a correlation between the neutralization potencies and nonneutralizing effector functions of bnAbs: PGT151 was positive for neutralization, ADCC, and binding to infected cells.
Berendam2021
(effector function, neutralization, binding affinity, broad neutralizer)
-
PGT151: To explore the ability of mice to generate neutralizing antibodies that target the HIV-1 fusion peptide (FP) with greater breadth and potency, this study tested 17 prime-boost regimens that utilized diverse FP-carrier conjugates and HIV-1 envelope trimers. Priming in mice with FP-carrier conjugates of variable peptide length elicited higher neutralizing responses, a result also confirmed in guinea pigs. From vaccinated mice, 21 mAbs, belonging to 4 distinct classes of FP-directed antibodies capable of cross-clade neutralization were isolated. Top antibodies from each class collectively neutralized over 50% of a 208-strain panel. Structural analyses revealed that each antibody class recognized a distinct conformation of FP and had a binding pocket capable of accommodating diverse FP. Murine vaccinations can thus elicit diverse neutralizing antibodies, and altering peptide length during prime can improve the elicitation of cross-clade responses targeting the FP. Previously-isolated FP-directed mAbs were used for comparison in a neutralization panel assay: VRC34.01, PGT151, ACS202, vFP1.01, vFP5.01, vFP7.04, vFP20.01, and vFP16.02.
Sastry2023
(antibody binding site, neutralization, vaccine antigen design, vaccine-induced immune responses, structure, broad neutralizer)
-
PGT151: X-ray and cryo-EM structures were derived for ACS202 with a fusion peptide (FP) and with a soluble Env trimer (AMC011 SOSIP.v4.2, derived from the same patient). The ACS202 CDRH3 forms a "b strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88. A cryo-EM structure of another previously identified bnAb, VRC34.01, with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP. The structures show that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles. The variable recognition of FP by bnAbs thus provides insights for vaccine design. The binding mechanism of ACS202 is compared with other FP antibodies (PGT151, VRC34.01, vFP16.02, and vFP20.01).
Yuan2019
(structure)
-
PGT151: Reduction in exposure of non-neutralizing Ab (nnAb) epitopes on native-like Env trimer immunogens results in bnAbs being elicited that have autologous tier 2 neutralization instead of tier 1. The design of trimer modifications to silence nnAb reactivity were directed towards (1) the V3 loop (2) epitopes exposed through CD4-induced conformational changes (CD4i epitopes) and (3) the exposed SOSIP trimer base that is usually buried within virus membrane. (1) In Steichen2016 2 Env variants of BG505 SOSIP.664 with reduced V3 nnAb-generating activity were created, one using mammalian display screens, BG505 MD39, and the other with an engineered disulfide bond, BG505 SOSIP.DS21. MD39's trimer design was improved by using the Rosetta Design platform and inserting 6 buried mutations to form BG505 Olio6, and both this trimer as well as the DS21 were shown to have reduced antigenicity for nnAb generation in a rabbit vaccine model. (2) To reduce CD4i epitope elicitation of nnAbs, saturation mutagenesis of Olio6 was performed, in search of the trimer that binds VRC01-class bnAbs but not CD4. BG505 Olio6.CD4KO containing the G473T mutation was identified. In addition, for the purposes of nucleic acid-based vaccine platform designs, the natural furin cleavage site between gp120 and gp41 was removed to abolish protease cleavage, by swapping the order of gp14 and gp120 in the gp160 gene, giving the trimer BG505 MD39.CP (circular permutation). (3) The exposed trimer base was masked with glycan in 3 under-glycosylated regions in order to direct bnAb responses to the distal regions (CD4bs, V2 apex, N332 superset) of the trimer instead, generating the GRSF MD39 and GRSF MD39.CP variants. Furthermore, variants with improved thermostability over MD39 were created, MD37 and MD64. All of these stabilizing mutations were transferred to diverse HIV isolates from different subtypes. Finally 3 subtype C (isolate 327c) trimers were assessed for binding to bnAbs, VRC01, PGT121, PGT151, PGT145, PG9 and to nnAbs, F105 and 17b - PGT151 did bind all three as well as BG505s SOSIP.664, MD39 and Olio6 and somewhat to AD8 MD64. PGT151 had reduced binding however to CP variant BG505 MD39.CP and GRSF trimer variants as well as AD8 SOSIP.
Kulp2017
(antibody binding site, antibody generation, antibody interactions, assay or method development, autologous responses, vaccine antigen design, structure)
-
PGT151: Most published structures of bnAbs, yet none of non- or poorly-neutralizing mAbs, were structurally compatible with a newly generated crystal structure of a mature ligand-free endoglycosidase H-treated BG505 SOSIP.664 Env trimer. Robust binding of the structurally incompatible V3- and CD4-bs targeting nAbs could be induced with CD4. A “DS” variant of BG505 SOSIP.664, containing a stabilizing disulfide bond between 201C and 433C mutations, was developed and appeared to represent an obligate intermediate in that it bound only a single CD4 and remained in a prefusion closed conformation. BnAb PGT151had KD values of 158 and 78.4 nM, respectively, when binding to BG505 SOSIP.664 wildtype and DS variant.
Kwon2015
(vaccine antigen design, binding affinity, structure)
-
PGT151: Native, well-ordered, soluble mimetics of the Env trimer from subtypes B (JRFL) and C (16055) were obtained from genetically identical samples of heterogeneous mixture of disordered Env SOSIPs. Negative selection by non-nAbs was used to remove disordered oligomers, leaving well-ordered trimers that were able to bind sCD4, a panel of bnAbs that bind CD4bs, and PGT151 which is a bnAb that binds only cleavage-dependent, well-ordered, Env trimer. Several biophysical techniques were used to interrogate the structure of the purified subtype B and C trimers.
Guenaga2015
(vaccine antigen design, subtype comparisons, structure)
-
PGT151: The study identified and characterized 5 neutralizing Ab lineages targeting the HIV-1 fusion peptide (FP) in vaccinated macaques. Genetic and structural analyses revealed that 2 of these lineages belong to an Ab class capable of neutralizing up to 59% of 208 diverse viral strains. Comparisons were made with the neutralization of previously-isolated FP mAbs, including ACS202, PGT151, vFP16.02, vFP20.01, and VRC34.01.
Kong2019
(antibody binding site, neutralization, binding affinity)
-
PGT151: This paper comprehensively defined the effect of every viable single aa mutation in the ectodomain and transmembrane domain of BG505.T332N Env on binding by 9 individual bnAbs targeting 5 epitope classes (VRC01, 3BNC117, PGT121, 10-1074, PG9, PGT145, PGT151, VRC34.01, and 10E8), as well as by a mixture of 3BNC117 and 10-1074. Escape mutations mostly occurred in a small subset of structurally-defined contacts within <4 Å and at sites within 5-10 Å of the Ab. Within the fusion peptide epitope, escape predominantly occurs at residues 512 and 514 for PGT151 but at residues 512-516 and nearby 518 for VRC34.01. Other Env sites with large cumulative mutational impacts on PGT151 binding were at the N611 glycosylation motif (N611 and S613). See LANL Features and Contacts database for more details. Strain-specific differences were also identified through comparisons of escape maps from PGT151 for a lab-derived Env (strain LAI, generated in this study) and primary isolate BF520.W14M.C2 (from Dingens2017, PMID 28579254).
Dingens2019
(antibody binding site, escape, subtype comparisons, contact residues)
-
PGT151: This study examined whether HIV-1-specific bnAbs are capable of cross-neutralizing simian immunodeficiency viruses (SIVs) from chimpanzees (n=11) or western gorillas (n=1). BnAbs directed against the epitopes at the CD4 binding site (VRC01, VRC03, VRC-PG04, VRC-CH03, VRC-CH31, F105, b13, NIH45-46G54W, 45-46m2, 45-46m7), V3 (10-1074, PGT121, PGT128, PGT135, and 2G12), and gp41-gp120 interface (8ANC195, 35O22, PGT151, PGT152, PGT158) failed to neutralize SIVcpz and SIVgor strains. V2-directed bNabs (PG9, PG16, PGT145) as well as llama-derived heavy-chain only antibodies recognizing the CD4 binding site or gp41 epitopes (JM4, J3, 3E3, 2E7, 11F1F, Bi-2H10) were either completely inactive or neutralized only a fraction of SIVcpz strains. In contrast, neutralization of SIVcpz and SIVgor strains was achieved with low-nanomolar potency by one antibody targeting the MPER region of gp41 (10E8), as well as functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Igmim2, CD4-218.3-E51, CD4-218.3-E51-mim2), mono- and bispecific anti-human CD4 mAbs (iMab, PG9-iMab, PG16-iMab, LM52, LM52-PGT128), and CCR5 receptor mAbs (PRO140, PRO140-10E8). Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5, and neutralized SIVcpz in chimpanzee CD4+ T cells. These findings provide new insight into the protective capacity of anti-HIV-1 bnAbs and identify candidates for further development to combat SIV infection.
Barbian2015
(neutralization, SIV, binding affinity)
-
PGT151: A recombinant native-like Env SOSIP trimer, AMC009, was developed based on viral founder sequences of elite neutralizer H18877. The subtype B AMC009 Env was defined as a Tier 2 virus based on a neutralization assay against well known nAbs (VRC01, 3BNC117, CH31, CH01, PG9, PG16, PGDM1400, 10-1074, PGT128, PGT121, PGT151, VRC34.01, 2G12, 2F5, 4E10, DH511.2.K3_4, 10E8, and the mAb mixture CH01-31).The AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bnAb epitopes. Its overall structure was similar to that of BG505 SOSIP.664, and it resembled one from another elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, AMC009 trimers did not induce autologous neutralizing antibody responses efficiently, while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the nAb activity from rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers.
Schorcht2020
(neutralization, vaccine-induced immune responses, structure)
-
PGT151: The study looked at the neutralization of subtype C Env sequences from 9 South African individuals followed longitudinally. A total of 43 Env sequences were cloned and assayed for neutralization by 12 bnAbs of various binding types (VRC07-LS, N6.LS, VRC01, PGT151, 10-1074 and PGT121, 10E8, 3BNC117, CAP256.VRC26.25, 4E10, PGDM1400, and N123-VRC34.01). Features associated with resistance to bNAbs were higher potential glycosylation sites, relatively longer V1 and V4 domains, and known signature mutations. The study found significant variability in the breadth and potency of bnAbs against circulating HIV-1 subtype C envelopes. In particular, VRC07-LS, N6.LS, VRC01, PGT151, 10-1074, and PGT121 display broad activity against subtype C variants. The results suggest that these 6 bnAbs are potent antibodies that should be considered for future antibody therapy and treatment studies targeting HIV-1 subtype C.
Mandizvo2022
(glycosylation, mutation acquisition, neutralization, immunotherapy)
-
PGT151: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); PGT151 had 17 improbable mutations out of 41 total AA mutations, and 0 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
-
PGT151: 14/17 cloned mAbs from mice, immunized with either modified native-like soluble Env trimer immunogen RC1 or RC1-4fill, and 32/38 cloned mAbs from macaques, immunized once with RC1-4fill multimerized on virus-like particles bound to the desired V3-glycan patch with diverse binding mechanisms. Germline usage and CDR sequence and length were identified for all 55 mAbs but only those with published functional characterization were included in this database. In macaques, these non-neutralizing mAbs had sequence and structural similarities to inferred germline precursors of bnAbs that target V3-glycan patch including longer light chain CDRs, CDRL3 QXXDSS & SYAG motifs, and CDRL1 NIG-like motifs. Compared to parental immunogen 11MUTB, both RC1 and RC1-4fill have N156 glycan deletion to facilitate V3-glycan patch binding while RC1-4fill also has glycans added at N230, N241, N289 and N344 to mask BG505-specific glycan hole. MAb PGT151 bound RC1, RC1-4fill and BG505 but at lower levels when compared to V3-glycan patch- or CD4bs-targeting mAbs. The inferred germline (iGL) revertant for PGT151 was not efficiently recognized by an anti-idiotypic Ab specific for the shared PGT121/10-1074 iGL revertant.
Escolano2019
(anti-idiotype)
-
PGT151: To understand early bnAb responses, 51 HIV-1 clade C infected infants were assayed for neutralization of a 12-virus multi-clade panel. Plasma bnAbs targeting V2-apex on Env were predominant in infant elite and broad neutralizers. In infant elite neutralizers, multi-variant infection was associated with plasma bnAbs targeting diverse autologous viruses. A panel of mAbs (PG9, PG16, PGT145, PGDM1400, VRC26.25, 10-1074, BG18, AIIMS-P01, PGT121, PGT128, PGT135, VRC01, N6, 3BNC117, PGT151, 35O22, 10E8, 4E10, F105, 17b, A32, 48d, b6, 447-52d) was assayed for their ability to neutralize Env clones from infant elite neutralizers; circulating viral variants in infant elite neutralizers were most susceptible to V2-apex bnAbs.
Mishra2020a
(neutralization, polyclonal antibodies)
-
PGT151: In vertically-infected infant AIIMS731, a rare HIV-1 mutation in hypervariable loop 2 (L184F) was studied. In patient sequences, this mutation was present in the majority of clones. A panel of 6 V2 bnAbs (PG9, PG16, PGT145, PGDM1400, CAP256.25, and CH01) was assayed for neutralization of 6 patient viral clones. The AIIMS731 viral variants segregated into 4 neutralization-sensitive and 2 resistant clones; sensitive clones carried 184F, while resistant clones carried the rare 184L mutation. A large panel of bnAbs targeting non-V2 epitopes was used to assess the neutralization of the 6 patient viral variants. The bnAb panel consisted of V3/N332 glycan supersite bnAbs (10-1074, BG18, AIIMS-P01, PGT121, PGT128, and PGT135), CD4bs bnAbs (VRC01, VRC03, VRC07-523LS, N6, 3BNC117, and NIH45-46 G54W), a silent face-targeting bnAb (PG05), fusion peptide and gp120-gp41 interface bnAbs (PGT151, 35O22, and N123-VRC34.01), and MPER bnAbs (10E8, 4E10, and 2F5). All of these bnAbs had similar neutralization efficiencies for all 6 clones, suggesting that the L184F mutation was specific for viral escape from neutralization by V2 apex bnAbs. A panel of non-neutralizing mAbs (V3 loop-targeting non-nAbs 447-52D and 19b, and CD4-induced non-nAbs 17b, A32, 48d, and b6), were also assessed; 2 of the variants (the same 2 susceptible to the V2 bnAbs) showed moderate neutralization by 447-52D, 19b, 17b, and 48d. The structure of ligand-free BG505 SOSIP trimer revealed that the side chain of L184 was outward facing and did not make significant intraprotomeric interactions, but upon mutating L184 to F184, a disruption of the accessible surface between the bulky side chain of F184 on one protomer and R165 on the neighboring protomer was seen. Thus, the L184F mutation resulted in increased susceptibility to neutralization by antibodies known to target the relatively more open conformation of Env on tier 1 viruses, suggesting that the rare L184F mutation allowed Env to sample more open states resembling the CD4-bound conformation where the CCR5 binding site is exposed.
Mishra2020
(neutralization, polyclonal antibodies)
-
PGT151: Analyses of all PDB HIV1-Env trimer (prefusion, closed) structures fulfilling certain parameters of resolution were performed to classify them on the basis of (a) antibody class which was informed by parental B cells as well as structural recognition, and (b) Env residues defining recognized HIV epitopes. Structural features of the 206 HIV epitope and bNAb paratopes were correlated with functional properties of the breadth and potency of neutralization against a 208-strain panel. Broadly nAbs with >25% breadth of neutralization belonged to 20 classes of antibodies with a large number of protruding loops and high degree of somatic hypermutation (SHM). Analysis of recognized HIV epitopes placed the bNAbs into 6 categories (viz. V1V2, glycan-V3, CD4-binding site, silent face center, fusion peptide and subunit interface). The epitopes contained high numbers of independent sequence segments and glycosylated surface area. PGT151-Env formed a distinct group within the fusion peptide category, Class PGT151. Structural data on PGT151 Fab complexed to cleaved wild type JR-FL ectodomain of the trimer was found in PDB ID: 5FUU.
Chuang2019
(antibody binding site, antibody interactions, neutralization, binding affinity, antibody sequence, structure, antibody lineage, broad neutralizer)
-
PGT151: An ART-naive HIV-controlling patient SA003 was found to have a high level of serum bNAb activity, and broadly neutralizing mAb LN01 IgG3 was isolated from patient serum. MAb PGT151 was used as a comparison in an assay of ADCC.
Pinto2019
(effector function)
-
PGT151: A novel CD4bs bnAb, 1-18, is identified with breadth (97% against a 119-strain multiclade panel) and potency exceeding (IC50 = 0.048 µg/mL) most VH1-46 and VH1-2 class bnAbs like 3BNC117, VRC01, N6, 8ANC131, 10-1074, PGT151, PGT121, 8ANC195, PG16 and PGDM1400. 1-18 effectively restricts viral escape better than bnAbs 3BNC117 and VRC01. As with VRC01-like Abs, 1-18 targets the CD4bs but it recognizes the epitope differently. Neutralizing activity against VRC01 Ab-class escapes is maintained by 1-18. In humanized mice infected by strain HIV-1YU2, viral suppression is also maintained by 1-18. VH1-46-derived B cell clone 4.1 from patient IDC561 produced potent, broadly active mAbs. Subclone 4.1 is characterized by a 6 aa CDRH1 insertion lengthening it from 8 to 14 aa and produces bNAbs 1-18 and 1-55. Cryo-EM at 2.5A of 1-18 in complex with BG505SOSIP.664 suggests their insertion increases inter-protomer contacts by a negatively charged DDDPYTDDD motif, resulting in an enlargement of the buried surface on HIV-1 gp120. Variations in glycosylation is thought to confer higher neutralizing activity on 1-18 over 1-55.
Schommers2020
(neutralization)
-
PGT151: 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 increase their effectiveness as a vaccine. PGT151 broadly neutralized HIV-1AD8 full-length and cytoplasmic tail-deleted Envs.
Castillo-Menendez2019
(vaccine antigen design, structure)
-
PGT151: 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)
-
PGT151: Two conserved tyrosine (Y) residues within the V2 loop of gp120, Y173 and Y177, were mutated individually or in combination, to either phenylalanine (F) or alanine (A) in several strains of diverse subtypes. In general, these mutations increased neutralization sensitivity, with a greater impact of Y177 over Y173 single mutations, of double over single mutations, and of A over F substitutions. The Y173A Y177A double mutation in HIV-1 BaL increased sensitivity to most of the weakly neutralizing MAbs tested (2158, 447-D, 268-D, B4e8, D19, 17b, 48d, 412d) and even rendered the virus sensitive to non-neutralizing antibodies against the CD4 binding site (F105, 654-30D, and b13). In the case of V2 mAb 697-30D, residue Y173 is part of its epitope, and thus abrogates its binding and has no effect on neutralization; the Y177A mutant alone did increase neutralization sensitivity to this mAb. When the double mutant was tested against bnAbs, there was a large decrease in neutralization sensitivity compared to WT for many bnAbs that target V1, V2, or V3 (PG9, PG16, VRC26.08, VRC38, PGT121, PGT122, PGT123, PGT126, PGT128, PGT130, PGT135, VRC24, CH103). The double mutation had lesser or no effect on neutralization by one V3 bnAb (2G12) and by most bnAbs targeting the CD4 binding site (VRC01, VRC07, VRC03, VRC-PG04, VRC-CH31, 12A12, 3BNC117, N6), the gp120-gp41 interface (35O22, PGT151), or the MPER (2F5, 4E10, 10E8).
Guzzo2018
(antibody binding site, neutralization)
-
PGT151: Without SOSIP changes, cleaved Env trimers disintegrate into their gp120 and gp41-ectodomain (gp41_ECTO) components. This study demonstrates that the gp41_ECTO component is the primary source of this Env metastability and that replacing wild-type gp41_ECTO with BG505 gp41_ECTO of the uncleaved prefusion-optimized design is a general and effective strategy for trimer stabilization. A panel of 11 bNAbs, including the gp120-gp41 interface recognized by PGT151 and 35O22, was used to assess conserved neutralizing epitopes on the trimer surface, and the main result was that the substitution was found to significantly improve trimer binding to bNAbs VRC01, PGT151, and 35O22, with P values (paired t test) of 0.0229, 0.0269, and 0.0407, respectively.
He2018
(antibody interactions, glycosylation, vaccine antigen design)
-
PGT151: To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and germline precursor bNAbs, the authors designed BG505 SOSIP.664 trimer variants whose V1 and V2 domains were stabilized by introducing disulfide bonds either within the V2 loop or between the V1 and V2 loops. The resulting SOSIP trimer variants — E153C/K178C, E153C/K178C/G152E and I184C/E190C — have improved reactivity with V2 bNAbs and their inferred germline precursors and are more sensitive to neutralization by V2 bNAbs. Compared with BG505 SOSIP.664, the E153C/R178C V1-V2 disulfide mutant bound the VRC01, PGT151, and 2G12 slightly less well and the G152E compensatory mutation improved VRC01, PGT151, and 2G12 binding. However, sensitivity to antibodies 2G12 and PGT151 was not affected for either mutant virus E153C/K178C/G152E or I184C/E190C.
deTaeye2019
(neutralization, vaccine antigen design, binding affinity)
-
PGT151: 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 1-preferring ligand PG151 recognized L193A variants of CH58 and CH77 IMCs with less efficiently compared to the WT.
Prevost2018
(effector function)
-
PGT151: The study describes a method, called mutational antigenic profiling, to comprehensively map all Env mutations that enable HIV to escape from broadly neutralizing antibody PGT151. The approach involves creating libraries of all single amino-acid Env mutants in the context of replication-competent HIV, selecting for mutations that promote antibody escape, and using deep sequencing to quantify the enrichment of each mutation. This method confirmed that mutations at previously identified sites (i.e. the disruption of glycosylation motifs at either 637 or 647) have clear effects on neutralization sensitivity but also showed strong selection at several sites where escape mutations have not previously been mapped.
Dingens2017
(neutralization, escape)
-
PGT151: This review discusses how the identification of super-antibodies, where and how such antibodies may be best applied and future directions for the field. PGT151, a prototype super-Ab, was isolated from human B cell clones. Antigenic region gp120–gp41 interface (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
PGT151: The effects of 16 glycoengineering (GE) methods on the sensitivities of 293T cell-produced pseudoviruses (PVs) to a large panel of bNAbs were investigated. Some bNAbs were dramatically impacted. PG9 and CAP256.09 were up to ˜30-fold more potent against PVs produced with co-transfected α-2,6 sialyltransferase. PGT151 and PGT121 were more potent against PVs with terminal sialic acids removed. 35O22 and CH01 were more potent against PV produced in GNT1-cells. The effects of GE on bNAbs VRC38.01, VRC13 and PGT145 were inconsistent between Env strains, suggesting context-specific glycan clashes. Overexpressing β-galactosyltransferase during PV production 'thinned' glycan coverage, by replacing complex glycans with hybrid glycans. This impacted PV sensitivity to some bNAbs. Maximum percent neutralization by excess bnAb was also improved by GE. Remarkably, some otherwise resistant PVs were rendered sensitive by GE. Germline-reverted versions of some bnAbs usually differed from their mature counterparts, showing glycan indifference or avoidance, suggesting that glycan binding is not germline-encoded but rather, it is gained during affinity maturation. Overall, these GE tools provided new ways to improve bnAb-trimer recognition that may be useful for informing the design of vaccine immunogens to try to elicit similar bnAbs.
Crooks2018
(vaccine antigen design, antibody lineage)
-
PGT151: 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. S306L plus R308L paired substitutions had no effect on the trimer reactivity of PGT151.
deTaeye2018
(broad neutralizer)
-
PGT151: DS-SOSIP.4mut (4mut) was identified as the most immunogenic and stable of 4 engineered, soluble, closed prefusion HIV-1 Env trimers. 4mut contained 4 mutations (M154, M300, M302 and L320) designed to form hydrophobic interactions between V1V1 and V3 loops. After V3-negative selection, gp41-gp120 interface-targeting mAb PGT151 recognized 4mut, the other 3 designed trimers (DS-SOSIP.6mut containing 4mut mutations, Y177W and I420M, DS-SOSIP.I423F and DS-SOSIP.A316W), and related trimers DS-SOSIP and BG505 SOSIP.664. Each DS-SOSIP variant was able to elicit trimer-specific responses, comparable to BG505 SOSIP.664, in guinea pigs after 4 immunizations, but none elicited heterologous neutralizing activity. Crystal structures were generated for 4mut and 6mut.
Chuang2017
(vaccine antigen design, vaccine-induced immune responses)
-
PGT151: Env trimers were engineered with selective deglycosylation around the CD4 binding site to see if they could be useful vaccine antigens. The neutralization of glycan-deleted trimers was tested for a set of bnAbs (PG9, PGT122, PGT135, b12, CH103, HJ16, VRC01, VRC13, PGT151, 8ANC195, 35O22), and the antigens elicited potent neutralization based on the CD4 supersite. A crystal structure was made of one of these Env trimers bound to Fabs 35O22 and 3H+109L. Guinea pigs vaccinated with these antigens achieved neutralization of deglycosylated Envs. Glycan-deleted Env trimers may be useful as priming antigens to increase the frequency of CD4 site-directed antibodies.
Zhou2017
(glycosylation, neutralization, vaccine antigen design, vaccine-induced immune responses)
-
PGT151: 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 PGT151), 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)
-
PGT151: The next generation of a computational neutralization fingerprinting (NFP) being used as a way to predict polyclonal Ab responses to HIV infection is presented. A new panel of 20 pseudoviruses, termed f61, was developed to aid in the assessment of experimental neutralization. This panel was used to assess 22 well-characterized bNAbs and mixtures thereof (HJ16, VRC01, 8ANC195, IGg1b12, PGT121, PGT128, PGT135, PG9, PGT151, 35O22, 10E8, 2F5, 4E10, VRC27, VRC-CH31, VRC-PG20, PG04, VRC23, 12A12, 3BNC117, PGT145, CH01). The new algorithms accurately predicted VRC01-like and PG9-like antibody specificities.
Doria-Rose2017
(neutralization, computational prediction)
-
PGT151: A weakly neutralizing antibody was isolated, CAP248-2B. The glycan dependence of CAP248-2B was compared to other known gp120-gp41 interface targeting bNAbs (8ANC195, 35O22, PGT151, 3BC315). CAP248-2B blocks the binding of 35O22, 3BC315, and PGT151 (but not 8ANC195 or 4E10) to cell surface envelope trimers.
Wibmer2017
(antibody interactions)
-
PGT151: 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. PGT151 and 8ANC195 were used as Abs that recognize the gp120-gp41 interface; they did not mediate strong ADCC activity.
Ding2015
(effector function)
-
PGT151: 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.
Crooks2015
(glycosylation, neutralization)
-
PGT151: This review classified and mapped the binding regions of 32 bNAbs isolated 2010-2016.
Wu2016
(review)
-
PGT151: This study produced Env SOSIP trimers for clades A (strain BG505), B (strain JR-FL), and G (strain X1193). Based on simulations, the MAb-trimer structures of all MAbs tested needed to accommodate at least one glycan, including both antibodies known to require specific glycans (PG9, PGT121, PGT135, 8ANC195, 35O22) and those that bind the CD4-binding site (b12, CH103, HJ16, VRC01, VRC13). A subset of monoclonal antibodies bound to glycan arrays assayed on glass slides (VRC26.09, PGT121, 2G12, PGT128, VRC13, PGT151, 35O22), while most of the antibodies did not have affinity for oligosaccharide in the context of a glycan array (PG9, PGT145, PGDM1400, PGT135, b12, CH103, HJ16, VRC16, VRC01, VRC-PG04, VRC-CH31, VRC-PG20, 3BNC60, 12A12, VRC18b, VRC23, VRC27, 1B2530, 8ANC131, 8ANC134, 8ANC195).
Stewart-Jones2016
(antibody binding site, glycosylation, structure)
-
PGT151: This review summarizes representative anti-HIV MAbs of the first generation (2G12, b12, 2F5, 4E10) and second generation (PG9, PG16, PGT145, VRC26.09, PGDM1400, PGT121, PGT124, PGT128, PGT135, 10-1074, VRC01, 3BNC117, CH103, PGT151, 35O22, 8ANC195, 10E8). Structures, epitopes, VDJ usage, CDR usage, and degree of somatic hypermutation are compared among these antibodies. The use of SOSIP trimers as immunogens to elicit B-cell responses is discussed.
Burton2016
(review, structure)
-
PGT151: 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. Otherwise NAb, anti gp120-gp41 PGT151, did not bind cell surface whether gp160 was missing C-terminal or not, and did not neutralize 92UG037.8 HIV-1 isolate either.
Chen2015
(neutralization, binding affinity)
-
PGT151: Factors that independently affect bNAb induction and evolution were identified as viral load, length of untreated infection, and viral diversity. Black subjects induced bNAbs more than white subjects, but this did not correlate with type of Ab response. Fingerprint analyses of induced bNAbs showed strong subtype dependency, with subtype B inducing significantly higher levels of CD4bs Abs and non-subtype B inducing V2-glycan specific Abs. Of the 239 bNAb antibody inducers found from 4,484 HIV-1 infected subjects,the top 105 inducers' neutralization fingerprint and epitope specificity was determined by comparison to the following antibodies - PG9, PG16, PGDM1400, PGT145 (V2 glycan); PGT121, PGT128, PGT130 (V3 glycan); VRC01, PGV04 (CD4bs) and PGT151 (interface) and 2F5, 4E10, 10E8 (MPER).
Rusert2016
(neutralization, subtype comparisons, broad neutralizer)
-
PGT151: PGT145 was used to positively isolate a subtype B Env trimer immunogen, B41 SOSIP.664-D7324, 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. All tested non-NAbs did not neutralize B41 (IC50 >50µg/ml). gp120-gp41ECTO interface glycan bNAb, PGT151, neutralized B41 psuedovirus.
Pugach2015
-
PGT151: The first generation of HIV trimer soluble immunogens, BG505 SOSIP.664 were tested in a mouse model for generation of nAb to neutralization-resistant circulating HIV strains. No such NAbs were induced, as mouse Abs targeted the bottom of soluble Env trimers, suggesting that the glycan shield of Env trimers is impenetrable to murine B cell receptors and that epitopes at the trimer base should be obscured in immunogen design in order to avoid non-nAb responses. Association and dissociation of known anti-trimer bNAbs (VRC01, PGT121, PGT128, PGT151, PGT135, PG9, 35O22, 3BC315 and PGT145) were found to be far greater than murine generated non-NAbs.
Hu2015
-
PGT151: A comprehensive antigenic map of the cleaved trimer BG505 SOSIP.664 was made by bNAb cross-competition. Epitope clusters at the CD4bs, quaternary V1/V2 glycan, N332-oligomannose patch and new gp120-gp41 interface and their interactions were delineated. Epitope overlap, proximal steric inhibition, allosteric inhibition or reorientation of glycans were seen in Ab cross-competition. Thus bNAb binding to trimers can affect surfaces beyond their epitopes. Among the gp120-gp41ECTO bNAbs, PGT151 strongly and bidirectionally competes 8ANC195 by steric hindrance since their epitopes do not overlap; but cannot compete 35O22. Surprisingly, PGT151 was competed out in a non-reciprocal manner by anti-V1/V2 glycan NAb, PGT145; while it strongly inhibited CD4-IgG2.
Derking2015
(antibody interactions, neutralization, binding affinity, structure)
-
PGT151: 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. The Clade C trimers and their pseudo typed virus have high affinity for the gp120-gp41 interface-binding PGT151.
Julien2015
(assay or method development, structure)
-
PGT151: 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 bNAb PGT151 to trimers was unaffected by trimer cross-linking.
Schiffner2016
(assay or method development, binding affinity, structure)
-
PGT151: The native-like, engineered trimer BG505 SOSIP.664 induced potent NAbs against conformational epitopes of neutralization-resistant Tier-2 viruses in rabbits and macaques, but induced cross-reactive NAbs against linear V3 epitopes of neutralization-sensitive Tier-1 viruses. A different trimer, B41 SOSIP.664 also induced strong autologous Tier-2 NAb responses in rabbits. Sera from 4/20 BG505 SOSIP.664-D7324 trimer-immunized rabbits were capable of inhibiting PGT151 binding to gp120-gp41 interface epitopes, but gp140-immunized and gp120-immunized sera could not.
Sanders2015
(antibody generation, neutralization, binding affinity, polyclonal antibodies)
-
PGT151: This study presents (i) a cryogenic electron microscopy (cryo-EM) structure of a clade B virus Env, lacking the cytoplasmic tail and stabilized by the broadly neutralizing antibody PGT151, at a resolution of 4.2 angstroms and (ii) a reconstruction of this form of Env in complex with PGT151 and MPER-targeting antibody 10E8 at a resolution of 8.8 angstroms. The PGT151 epitope includes the fusion peptide and an extensive network of primary and secondary glycan interactions that stabilize the prefusion conformation of the Env trimer.
Lee2016
(glycosylation, structure)
-
PGT151: This paper analyzed site-specific glycosylation of a soluble, recombinant trimer (BG505 SOSIP.664). This trimer mapped the extremes of simplicity and diversity of glycan processing at individual sites and revealed a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, they identified examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens. Neutralization profiles for gp120/gp41interface Ab, PG151, to multiple epitopes were determined.
Behrens2016
(antibody binding site, glycosylation)
-
PGT151: 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-gp41ECTO protomer) and several mAbs, both neutralizing (VRC01, PGV04, PG9, PG16, PGT121, PGT122, PGT123, PGT145, PGT151, 2G12) and non-neutralizing (b6, b12, 14e, 19b, F240). PGT151 bNAb, that binds to a novel epitope at the gp120-gp41 interface, bound the trimer, the protomer less well and the monomer not at all.
Yasmeen2014
(antibody binding site, assay or method development)
-
PGT151: Ten mAbs were isolated from a vertically-infected infant BF520 at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bNAbs derived from adults, but its potency was lower. BF520.1 was shown to target the base of the V3 loop at the N332 supersite. gp120-gp41 interface-binding, first generation mAb, PGT151 when compared had a geometric mean of IC50=0.17 µg/ml for 5/12 viruses it neutralized at a potency of 42%. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody binding site, neutralization, responses in children, structure)
-
PGT151: The neutralization of 14 bnAbs was assayed against a global panel of 12 or 17 Env pseudoviruses. From IC50, IC80, IC90, and IC99 values, the slope of the dose-response curve was calculated. Each class of Ab had a fairly consistent slope. Neutralization breadth was strongly correlated with slope. An IIP (Instantaneous Inhibitory Potential) value was calculated, based on both the slope and IC50, and this value may be predictive of clinical efficacy. PGT151, a gp120/gp41 glycan bnAb belonged to a group with slopes <1.
Webb2015
(neutralization)
-
PGT151: This study evaluated the binding of 15 inferred germline (gl) precursors of bNAbs that are directed to different epitope clusters, to 3 soluble native-like SOSIP.664 Env trimers - BG505, B41 and ZM197M. The trimers bound to some gl precursors, particularly those of V1V2-targeted Abs. These trimers may be useful for designing immunogens able to target gl precursors. gp41 and interface-binding gl-PGT151 precursor did not bind any trimers.
Sliepen2015
(binding affinity, antibody lineage)
-
PGT151: 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)
-
PGT151: The newly identified and defined epitope for PGT151 family MAbs binds to a site of vulnerability that does not overlap with any other bnAb epitopes. The complex PGT151 epitope requires gp160 cleavage, a properly formed quarternary gp120-gp41 interface, and fully processed gp41 glycans (complex forms). The residues that influence binding are K490, T499, R500, R503 in gp120 C5 region and K601, N607, N611, N637 in gp41.
Blattner2014
(antibody binding site, glycosylation, structure)
-
PGT151: 8 bNAbs (PGT151 family) were isolated from an elite neutralizer. The new bNAbs bind a previously unknown glycan-dependent epitope on the prefusion conformation of gp41. These MAbs are specific for the cleaved Env trimer and do not recognize uncleaved Env trimer. The epitope involves highly conserved N-glycosylation sites N611 and N637 and a residue E647. The relative residues' contributions are isolate-dependent. PGT151 neutralization was adversely affected by N611 substitution, and abrogated by N611+N637 or N611+E647 substitutions. PGT151 showed 1 log higher neutralization potency than PG9, neutralized 66% of 117 cross-clade isolates, was not polyreactive and mediated ADCC.
Falkowska2014
(antibody binding site, antibody generation, effector function, glycosylation, broad neutralizer)
References
Showing 63 of
63 references.
Isolation Paper
Falkowska2014
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Barbian2015
Hannah J. Barbian, Julie M. Decker, Frederic Bibollet-Ruche, Rachel P. Galimidi, Anthony P. West, Jr., Gerald H. Learn, Nicholas F. Parrish, Shilpa S. Iyer, Yingying Li, Craig S. Pace, Ruijiang Song, Yaoxing Huang, Thomas N. Denny, Hugo Mouquet, Loic Martin, Priyamvada Acharya, Baoshan Zhang, Peter D. Kwong, John R. Mascola, C. Theo Verrips, Nika M. Strokappe, Lucy Rutten, Laura E. McCoy, Robin A. Weiss, Corrine S. Brown, Raven Jackson, Guido Silvestri, Mark Connors, Dennis R. Burton, George M. Shaw, Michel C. Nussenzweig, Pamela J. Bjorkman, David D. Ho, Michael Farzan, and Beatrice H. Hahn. Neutralization Properties of Simian Immunodeficiency Viruses Infecting Chimpanzees and Gorillas. mBio, 6(2), 21 Apr 2015. PubMed ID: 25900654.
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Behrens2016
Anna-Janina Behrens, Snezana Vasiljevic, Laura K. Pritchard, David J. Harvey, Rajinder S. Andev, Stefanie A. Krumm, Weston B. Struwe, Albert Cupo, Abhinav Kumar, Nicole Zitzmann, Gemma E. Seabright, Holger B. Kramer, Daniel I. R. Spencer, Louise Royle, Jeong Hyun Lee, Per J. Klasse, Dennis R. Burton, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, John P. Moore, Katie J. Doores, and Max Crispin. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep., 14(11):2695-2706, 22 Mar 2016. PubMed ID: 26972002.
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Berendam2021
Stella J. Berendam, Tiffany M. Styles, Papa K.. Morgan-Asiedu, DeAnna Tenney, Amit Kumar, Veronica Obregon-Perko, Katharine J. Bar, Kevin O. Saunders, Sampa Santra, Kristina De Paris, Georgia D. Tomaras, Ann Chahroudi, Sallie R. Permar, Rama R. Amara, and Genevieve G. Fouda. Systematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency Viruses. J. Virol., 95(3), 13 Jan 2021. PubMed ID: 33177194.
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Blattner2014
Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, and Andrew B. Ward. Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers. Immunity, 40(5):669-680, 15 May 2014. PubMed ID: 24768348.
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Burton2016
Dennis R. Burton and Lars Hangartner. Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design. Annu. Rev. Immunol., 34:635-659, 20 May 2016. PubMed ID: 27168247.
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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.
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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.
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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.
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Chuang2017
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G. Wanninger, Yongping Yang, Nicole A. Doria-Rose, Ivelin S. Georgiev, Jason Gorman, M. Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J. Virol., 91(10), 15 May 2017. PubMed ID: 28275193.
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Chuang2019
Gwo-Yu Chuang, Jing Zhou, Priyamvada Acharya, Reda Rawi, Chen-Hsiang Shen, Zizhang Sheng, Baoshan Zhang, Tongqing Zhou, Robert T. Bailer, Venkata P. Dandey, Nicole A. Doria-Rose, Mark K. Louder, Krisha McKee, John R. Mascola, Lawrence Shapiro, and Peter D. Kwong. Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition. Structure, 27(1):196-206.e6, 2 Jan 2019. PubMed ID: 30471922.
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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.
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Crooks2018
Ema T. Crooks, Samantha L. Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Ramisch, Sergey Menis, William R. Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R. Mascola, Gestur Vidarsson, and James M. Binley. Glycoengineering HIV-1 Env Creates `Supercharged' and `Hybrid' Glycans to Increase Neutralizing Antibody Potency, Breadth and Saturation. PLoS Pathog., 14(5):e1007024, May 2018. PubMed ID: 29718999.
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Derking2015
Ronald Derking, Gabriel Ozorowski, Kwinten Sliepen, Anila Yasmeen, Albert Cupo, Jonathan L. Torres, Jean-Philippe Julien, Jeong Hyun Lee, Thijs van Montfort, Steven W. de Taeye, Mark Connors, Dennis R. Burton, Ian A. Wilson, Per-Johan Klasse, Andrew B. Ward, John P. Moore, and Rogier W. Sanders. Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer. PLoS Pathog, 11(3):e1004767, Mar 2015. PubMed ID: 25807248.
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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.
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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.
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deTaeye2019
Steven W. de Taeye, Eden P. Go, Kwinten Sliepen, Alba Torrents de la Peña, Kimberly Badal, Max Medina-Ramírez, Wen-Hsin Lee, Heather Desaire, Ian A. Wilson, John P. Moore, Andrew B. Ward, and Rogier W. Sanders. Stabilization of the V2 Loop Improves the Presentation of V2 Loop-Associated Broadly Neutralizing Antibody Epitopes on HIV-1 Envelope Trimers. J. Biol. Chem., 294(14):5616-5631, 5 Apr 2019. PubMed ID: 30728245.
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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.
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Dingens2017
Adam S. Dingens, Hugh K. Haddox, Julie Overbaugh, and Jesse D. Bloom. Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody. Cell Host Microbe, 21(6):777-787.e4, 14 Jun 2017. PubMed ID: 28579254.
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Dingens2019
Adam S. Dingens, Dana Arenz, Haidyn Weight, Julie Overbaugh, and Jesse D. Bloom. An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes. Immunity, 50(2):520-532.e3, 19 Feb 2019. PubMed ID: 30709739.
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Doria-Rose2017
Nicole A. Doria-Rose, Han R. Altae-Tran, Ryan S. Roark, Stephen D. Schmidt, Matthew S. Sutton, Mark K. Louder, Gwo-Yu Chuang, Robert T. Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S. Abdool Karim, James M. Binley, Mark Connors, Barton F. Haynes, Malcolm A. Martin, David C. Montefiori, Lynn Morris, Julie Overbaugh, Peter D. Kwong, John R. Mascola, and Ivelin S. Georgiev. Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting. PLoS Pathog., 13(1):e1006148, Jan 2017. PubMed ID: 28052137.
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Escolano2019
Amelia Escolano, Harry B. Gristick, Morgan E. Abernathy, Julia Merkenschlager, Rajeev Gautam, Thiago Y. Oliveira, Joy Pai, Anthony P. West, Jr., Christopher O. Barnes, Alexander A. Cohen, Haoqing Wang, Jovana Golijanin, Daniel Yost, Jennifer R. Keeffe, Zijun Wang, Peng Zhao, Kai-Hui Yao, Jens Bauer, Lilian Nogueira, Han Gao, Alisa V. Voll, David C. Montefiori, Michael S. Seaman, Anna Gazumyan, Murillo Silva, Andrew T. McGuire, Leonidas Stamatatos, Darrell J. Irvine, Lance Wells, Malcolm A. Martin, Pamela J. Bjorkman, and Michel C. Nussenzweig. Immunization Expands B Cells Specific to HIV-1 V3 Glycan in Mice and Macaques. Nature, 570(7762):468-473, Jun 2019. PubMed ID: 31142836.
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Guenaga2015
Javier Guenaga, Natalia de Val, Karen Tran, Yu Feng, Karen Satchwell, Andrew B. Ward, and Richard T. Wyatt. Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-Like Properties. PLoS Pathog., 11(1):e1004570, Jan 2015. PubMed ID: 25569572.
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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.
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He2018
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward, David Nemazee, Dennis R. Burton, Ian A. Wilson, and Jiang Zhu. HIV-1 Vaccine Design through Minimizing Envelope Metastability. Sci. Adv., 4(11):eaau6769, Nov 2018. PubMed ID: 30474059.
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Hu2015
Joyce K. Hu, Jordan C. Crampton, Albert Cupo, Thomas Ketas, Marit J. van Gils, Kwinten Sliepen, Steven W. de Taeye, Devin Sok, Gabriel Ozorowski, Isaiah Deresa, Robyn Stanfield, Andrew B. Ward, Dennis R. Burton, Per Johan Klasse, Rogier W. Sanders, John P. Moore, and Shane Crotty. Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity. J. Virol., 89(20):10383-10398, Oct 2015. PubMed ID: 26246566.
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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.
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Kong2019
Rui Kong, Hongying Duan, Zizhang Sheng, Kai Xu, Priyamvada Acharya, Xuejun Chen, Cheng Cheng, Adam S. Dingens, Jason Gorman, Mallika Sastry, Chen-Hsiang Shen, Baoshan Zhang, Tongqing Zhou, Gwo-Yu Chuang, Cara W. Chao, Ying Gu, Alexander J. Jafari, Mark K. Louder, Sijy O'Dell, Ariana P. Rowshan, Elise G. Viox, Yiran Wang, Chang W. Choi, Martin M. Corcoran, Angela R. Corrigan, Venkata P. Dandey, Edward T. Eng, Hui Geng, Kathryn E. Foulds, Yicheng Guo, Young D. Kwon, Bob Lin, Kevin Liu, Rosemarie D. Mason, Martha C. Nason, Tiffany Y. Ohr, Li Ou, Reda Rawi, Edward K. Sarfo, Arne Schön, John P. Todd, Shuishu Wang, Hui Wei, Winston Wu, NISC Comparative Sequencing Program, James C. Mullikin, Robert T. Bailer, Nicole A. Doria-Rose, Gunilla B. Karlsson Hedestam, Diana G. Scorpio, Julie Overbaugh, Jesse D. Bloom, Bridget Carragher, Clinton S. Potter, Lawrence Shapiro, Peter D. Kwong, and John R. Mascola. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Cell, 178(3):567-584.e19, 25 Jul 2019. PubMed ID: 31348886.
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Kulp2017
Daniel W. Kulp, Jon M. Steichen, Matthias Pauthner, Xiaozhen Hu, Torben Schiffner, Alessia Liguori, Christopher A. Cottrell, Colin Havenar-Daughton, Gabriel Ozorowski, Erik Georgeson, Oleksandr Kalyuzhniy, Jordan R. Willis, Michael Kubitz, Yumiko Adachi, Samantha M. Reiss, Mia Shin, Natalia de Val, Andrew B. Ward, Shane Crotty, Dennis R. Burton, and William R. Schief. Structure-Based Design of Native-Like HIV-1 Envelope Trimers to Silence Non-Neutralizing Epitopes and Eliminate CD4 Binding. Nat. Commun., 8(1):1655, 21 Nov 2017. PubMed ID: 29162799.
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Kwon2015
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S. Georgiev, Emma T. Crooks, Jason Gorman, M. Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S. Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Mark A. Hallen, Adam Harned, Tatsiana Kirys, Mark K. Louder, Sijy O'Dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume B. E. Stewart-Jones, Jonathan Stuckey, Paul V. Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R. Donald, Lawrence K. Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K. Lee, James Arthos, James B. Munro, Scott C. Blanchard, Walther Mothes, James M. Binley, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env. Nat. Struct. Mol. Biol., 22(7):522-531, Jul 2015. PubMed ID: 26098315.
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Lee2016
Jeong Hyun Lee, Gabriel Ozorowski, and Andrew B. Ward. Cryo-EM Structure of a Native, Fully Glycosylated, Cleaved HIV-1 Envelope Trimer. Science, 351(6277):1043-1048, 4 Mar 2016. PubMed ID: 26941313.
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Mandizvo2022
Tawanda Mandizvo, Nombali Gumede, Bongiwe Ndlovu, Siphiwe Ndlovu, Jaclyn K. Mann, Denis R. Chopera, Lanish Singh, Krista L. Dong, Bruce D. Walker, Zaza M. Ndhlovu, Christy L. Lavine, Michael S. Seaman, Kamini Gounder, and Thumbi Ndung'u. Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection. J. Virol., 96(24):e0127022, 21 Dec 2022. PubMed ID: 36453881.
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Mishra2020
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Bimal Kumar Das, Sushil Kumar Kabra, Rakesh Lodha, and Kalpana Luthra. A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex. J. Virol., 94(19), 15 Sep 2020. PubMed ID: 32669335.
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Mishra2020a
Nitesh Mishra, Shaifali Sharma, Ayushman Dobhal, Sanjeev Kumar, Himanshi Chawla, Ravinder Singh, Muzamil Ashraf Makhdoomi, Bimal Kumar Das, Rakesh Lodha, Sushil Kumar Kabra, and Kalpana Luthra. Broadly Neutralizing Plasma Antibodies Effective against Autologous Circulating Viruses in Infants with Multivariant HIV-1 Infection. Nat. Commun., 11(1):4409, 2 Sep 2020. PubMed ID: 32879304.
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Molinos-Albert2023
Luis M. Molinos-Albert, Eduard Baquero, Melanie Bouvin-Pley, Valerie Lorin, Caroline Charre, Cyril Planchais, Jordan D. Dimitrov, Valerie Monceaux, Matthijn Vos, Laurent Hocqueloux, Jean-Luc Berger, Michael S. Seaman, Martine Braibant, Veronique Avettand-Fenoel, Asier Saez-Cirion, and Hugo Mouquet. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller. Cell Host Microbe, 31(8):1275-1287e8 doi, Aug 2023. PubMed ID: 37433296
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Moyo2018
Thandeka Moyo, June Ereño-Orbea, Rajesh Abraham Jacob, Clara E. Pavillet, Samuel Mundia Kariuki, Emily N. Tangie, Jean-Philippe Julien, and Jeffrey R. Dorfman. Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11. J. Virol., 92(14), 15 Jul 2018. PubMed ID: 29618644.
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Pinto2019
Dora Pinto, Craig Fenwick, Christophe Caillat, Chiara Silacci, Serafima Guseva, François Dehez, Christophe Chipot, Sonia Barbieri, Andrea Minola, David Jarrossay, Georgia D. Tomaras, Xiaoying Shen, Agostino Riva, Maciej Tarkowski, Olivier Schwartz, Timothée Bruel, Jérémy Dufloo, Michael S. Seaman, David C. Montefiori, Antonio Lanzavecchia, Davide Corti, Giuseppe Pantaleo, and Winfried Weissenhorn. Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01. Cell Host Microbe, 26(5):623-637.e8, 13 Nov 2019. PubMed ID: 31653484.
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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.
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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.
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Rusert2016
Peter Rusert, Roger D. Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L. Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W. Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R. Regoes, Huldrych F. Günthard, Alexandra Trkola, and Swiss HIV Cohort Study. Determinants of HIV-1 Broadly Neutralizing Antibody Induction. Nat. Med., 22(11):1260-1267, Nov 2016. PubMed ID: 27668936.
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Sanders2015
Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-Ramírez, Jaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia LaBranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, and John P. Moore. HIV-1 Neutralizing Antibodies Induced by Native-Like Envelope Trimers. Science, 349(6244):aac4223, 10 Jul 2015. PubMed ID: 26089353.
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Sastry2023
Mallika Sastry, Anita Changela, Jason Gorman, Kai Xu, Gwo-Yu Chuang, Chen-Hsiang Shen, Cheng Cheng, Hui Geng, Sijy O'Dell, Li Ou, Reda Rawi, Mateo Reveiz, Guillaume B. E. Stewart-Jones, Shuishu Wang, Baoshan Zhang, Tongqing Zhou, Andrea Biju, Michael Chambers, Xuejun Chen, Angela R. Corrigan, Bob C. Lin, Mark K. Louder, Krisha McKee, Alexandra F. Nazzari, Adam S. Olia, Danealle K. Parchment, Edward K. Sarfo, Tyler Stephens, Jonathan Stuckey, Yaroslav Tsybovsky, Raffaello Verardi, Yiran Wang, Cheng-Yan Zheng, Yuling Chen, Nicole A. Doria-Rose, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization. J. Virol., 97(5):e0160422, 31 May 2023. PubMed ID: 37098956.
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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.
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Schommers2020
Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara Lehmann, Gerd Fätkenheuer, Michael S. Seaman, Jesse D. Bloom, Pamela J. Bjorkman, and Florian Klein. Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. Cell, 180(3):471-489.e22, 6 Feb 2020. PubMed ID: 32004464.
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Schorcht2020
Anna Schorcht, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, Judith A. Burger, Steven W. de Taeye, Alba Torrents de la Peña, Ilja Bontjer, Stephanie Gumbs, Gabriel Ozorowski, Celia C. LaBranche, Natalia de Val, Anila Yasmeen, Per Johan Klasse, David C. Montefiori, John P. Moore, Hanneke Schuitemaker, Max Crispin, Marit J. van Gils, Andrew B. Ward, and Rogier W. Sanders. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J. Virol., 94(24), 23 Nov 2020. PubMed ID: 32999024.
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Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
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Sliepen2015
Kwinten Sliepen, Max Medina-Ramirez, Anila Yasmeen, John P. Moore, Per Johan Klasse, and Rogier W. Sanders. Binding of Inferred Germline Precursors of Broadly Neutralizing HIV-1 Antibodies to Native-Like Envelope Trimers. Virology, 486:116-120, Dec 2015. PubMed ID: 26433050.
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Sliepen2019
Kwinten Sliepen, Byung Woo Han, Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia van der Woude, Alba Torrents de la Pena, Marielle J. van Breemen, Juan Miguel Camacho-Sanchez, Judith A. Burger, Max Medina-Ramirez, Nuria Gonzalez, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. van Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson, and Rogier W. Sanders. Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Nat Commun, 10(1):2355 doi, May 2019. PubMed ID: 31142746
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Stewart-Jones2016
Guillaume B. E. Stewart-Jones, Cinque Soto, Thomas Lemmin, Gwo-Yu Chuang, Aliaksandr Druz, Rui Kong, Paul V. Thomas, Kshitij Wagh, Tongqing Zhou, Anna-Janina Behrens, Tatsiana Bylund, Chang W. Choi, Jack R. Davison, Ivelin S. Georgiev, M. Gordon Joyce, Young Do Kwon, Marie Pancera, Justin Taft, Yongping Yang, Baoshan Zhang, Sachin S. Shivatare, Vidya S. Shivatare, Chang-Chun D. Lee, Chung-Yi Wu, Carole A. Bewley, Dennis R. Burton, Wayne C. Koff, Mark Connors, Max Crispin, Ulrich Baxa, Bette T. Korber, Chi-Huey Wong, John R. Mascola, and Peter D. Kwong. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell, 165(4):813-826, 5 May 2016. PubMed ID: 27114034.
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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.
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Walker2018
Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211.
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Wang2023
Shuishu Wang, Flavio Matassoli, Baoshan Zhang, Tracy Liu, Chen-Hsiang Shen, Tatsiana Bylund, Timothy Johnston, Amy R. Henry, I-Ting Teng, Prabhanshu Tripathi, Jordan E. Becker, Anita Changela, Ridhi Chaudhary, Cheng Cheng, Martin Gaudinski, Jason Gorman, Darcy R. Harris, Myungjin Lee, Nicholas C. Morano, Laura Novik, Sijy O'Dell, Adam S. Olia, Danealle K. Parchment, Reda Rawi, Jesmine Roberts-Torres, Tyler Stephens, Yaroslav Tsybovsky, Danyi Wang, David J. Van Wazer, Tongqing Zhou, Nicole A. Doria-Rose, Richard A. Koup, Lawrence Shapiro, Daniel C. Douek, Adrian B. McDermott, and Peter D. Kwong. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Cell Rep, 42(7):112755 doi, Jul 2023. PubMed ID: 37436899
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Ward2019
Andrew B. Ward. Playing Chess with HIV. Immunity, 50(2):283-285 doi, Feb 2019. PubMed ID: 30784575
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Webb2015
Nicholas E. Webb, David C. Montefiori, and Benhur Lee. Dose-Response Curve Slope Helps Predict Therapeutic Potency and Breadth of HIV Broadly Neutralizing Antibodies. Nat. Commun., 6:8443, 29 Sep 2015. PubMed ID: 26416571.
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Wibmer2017
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N. Bhiman, Daniel J. Sheward, Debra H. Elliott, Julie Rouelle, Ashley Smira, M. Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R. Burton, Mark Connors, Salim S. Abdool Karim, John R. Mascola, James E. Robinson, Andrew B. Ward, Carolyn Williamson, Peter D. Kwong, Lynn Morris, and Penny L. Moore. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape. PLoS Pathog., 13(1):e1006074, Jan 2017. PubMed ID: 28076415.
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Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
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Willis2022
Jordan R. Willis, Zachary T. Berndsen, Krystal M. Ma, Jon M. Steichen, Torben Schiffner, Elise Landais, Alessia Liguori, Oleksandr Kalyuzhniy, Joel D. Allen, Sabyasachi Baboo, Oluwarotimi Omorodion, Jolene K. Diedrich, Xiaozhen Hu, Erik Georgeson, Nicole Phelps, Saman Eskandarzadeh, Bettina Groschel, Michael Kubitz, Yumiko Adachi, Tina-Marie Mullin, Nushin B. Alavi, Samantha Falcone, Sunny Himansu, Andrea Carfi, Ian A. Wilson, John R. Yates III, James C. Paulson, Max Crispin, Andrew B. Ward, and William R. Schief. Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors. Immunity, 55(11):2149-2167e9 doi, Nov 2022. PubMed ID: 36179689
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Wu2016
Xueling Wu and Xiang-Peng Kong. Antigenic Landscape of the HIV-1 Envelope and New Immunological Concepts Defined by HIV-1 Broadly Neutralizing Antibodies. Curr. Opin. Immunol., 42:56-64, Oct 2016. PubMed ID: 27289425.
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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.
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Yuan2019
Meng Yuan, Christopher A. Cottrell, Gabriel Ozorowski, Marit J. van Gils, Sonu Kumar, Nicholas C. Wu, Anita Sarkar, Jonathan L. Torres, Natalia de Val, Jeffrey Copps, John P. Moore, Rogier W. Sanders, Andrew B. Ward, and Ian A. Wilson. Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies. Cell Host Microbe, 25(6):873-883.e5, 12 Jun 2019. PubMed ID: 31194940.
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Zhou2017
Tongqing Zhou, Nicole A. Doria-Rose, Cheng Cheng, Guillaume B. E. Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D. Schmidt, Kai Xu, Lei Chen, Rita E. Chen, Mark K. Louder, Marie Pancera, Timothy G. Wanninger, Baoshan Zhang, Anqi Zheng, S. Katie Farney, Kathryn E. Foulds, Ivelin S. Georgiev, M. Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F. Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G. Scorpio, Lawrence Shapiro, Adrian B. McDermott, John R. Mascola, and Peter D. Kwong. Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep., 19(4):719-732, 25 Apr 2017. PubMed ID: 28445724.
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Sengupta2023
Srona Sengupta, Josephine Zhang, Madison C. Reed, Jeanna Yu, Aeryon Kim, Tatiana N. Boronina, Nathan L. Board, James O. Wrabl, Kevin Shenderov, Robin A. Welsh, Weiming Yang, Andrew E. Timmons, Rebecca Hoh, Robert N. Cole, Steven G. Deeks, Janet D. Siliciano, Robert F. Siliciano, and Scheherazade Sadegh-Nasseri. A cell-free antigen processing system informs HIV-1 epitope selection and vaccine design. J Exp Med, 220(7):e20221654 doi, Jul 2023. PubMed ID: 37058141
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Richard2018
Jonathan Richard, Jeremie Prevost, Nirmin Alsahafi, Shilei Ding, and Andres Finzi. Impact of HIV-1 Envelope Conformation on ADCC Responses. Trends Microbiol, 26(4):253-265 doi, Apr 2018. PubMed ID: 29162391
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