Found 1 matching record:
Displaying record number 3044
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MAb ID |
VRC26.07 (CAP256-VRC26.07) |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env(160-169) |
Epitope |
|
Ab Type |
gp120 V2 // V2 glycan(V2g) // V2 apex, quaternary structure |
Neutralizing |
P View neutralization details |
Contacts and Features |
View contacts and features |
Species
(Isotype)
|
human |
Patient |
CAP256 |
Immunogen |
HIV-1 infection |
Country |
South Africa |
Keywords |
antibody binding site, antibody generation, antibody lineage, antibody sequence, autologous responses, broad neutralizer, escape, glycosylation, mutation acquisition, neutralization, review, structure, superinfection |
Notes
Showing 7 of
7 notes.
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VRC26.07: This study followed the evolution of VRC26 lineage to investigate the phenotypic changes of the virus populations during the early phases of bnAb induction. Longitudinal viruses that evolved from the VRC26-resistant primary infecting (PI) virus, the VRC26-sensitive superinfecting (SU) virus, and ensuing PI-SU recombinants revealed substantial phenotypic changes in Env, with a switch in Env properties, coinciding with resistance to VRC26 mAbs. Twelve of the VRC26 bnAbs (VRC26.01, VRC26.05, VRC26.06, VRC26.07, VRC26.08, VRC26.09, VRC26.10, VRC26.12, VRC26.17, VRC26.21, VRC26.25, VRC26.31) were assayed for neutralization of autologous Envs; in general, they were effective in neutralizing the SU-like viruses, less effective for the PI-like viruses, and were ineffective against the PI/SU recombinant forms. Decreased sensitivity of SU-like viruses was linked with reduced infectivity, altered entry kinetics, and lower sensitivity to neutralization after CD4 attachment. The VRC26 lineage maintained neutralization activity against cell-associated CAP256 virus, indicating that cell-cell transmission is not a dominant escape pathway. Reduced fitness of the early escape variants and sustained sensitivity in cell-cell transmission are both features that limit virus replication, thereby impeding rapid escape. This supports a scenario where VRC26 lineage mAbs allowed only partial viral escape for a prolonged period, possibly increasing the time window for bnAb maturation.
Reh2018
(autologous responses, neutralization, escape, antibody lineage)
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VRC26.07: The maturation features of the HIV-neutralizing anti-V1V2 VRC26 lineage by simultaneously sequencing the exon together with the downstream intron of VRC26 members is reported. Multiple events of amino acid mutational convergence in the CDR3 of VRC26 members have been identified using the mutational landscapes of both segments and the selection-free nature of the intron and determined potential intermediates with diverse CDR3s to a late stage bNAb from 2 years prior to its isolation region. Timeline of all tested Abs from the VRC26 lineage is shown for the two major bifurcating branches (Fig 5).
Johnson2018
(mutation acquisition, antibody lineage)
-
CAP256-VRC26.07: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. Recombinant native-like HIV Env trimers have enabled the identification of CAP256-VRC26.07, a potent ‘PG9-class’ bNAb. Antigenic region V2 apex (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
VRC26.07: The development of broad neutralization was studied by examining both the viral variants of superinfected donor CAP256 and the phylogeny and neutralization of the 33 CAP256-VRC26 V1/V2 lineage mAbs. Two members (VRC26.01 and VRC26.24) formed a "dead end" sublineage with restricted breadth. A larger sublineage containing the other mAbs displayed extensive evolution, suggesting adaptation in response to emerging viral escape mutations, particularly at residues 166 and 169. Early viral escape at key antibody-virus contact sites selects for Ab sublineages that can tolerate these changes and thus evolve Abs with broad neutralization breadth. CAP256-VRC26.07 neutralized superinfecting virus and mutant K169R at <0.02µg/ml, and other position 169 and 166 mutants at <50µg/ml. It had a neutralization breadth of ˜10%.
Bhiman2015
(escape, antibody lineage)
-
VRC26.07: Twenty-one new members of the CAP256-VRC26 lineage were isolated from donor CAP256 from time points of peak serum neutralization breadth and potency; 3 of them have a broader neutralization capacity than previously isolated family members. The most potent was CAP256-VRC26.25, which displayed a 10-fold greater neutralization potency than previously described lineage members. It neutralized 57% of diverse clade viral isolates and 70% of clade C isolates. The mechanism of its outstanding potency may relate to its reduced dependence on N160 glycan or its unique, long CDRH3 conformation. The epitope recognized by the new CAP256-VRC26 antibodies is similar to that recognized by the previously described relatives, and centers on Env 166-169. With a 46-pseudo- plus 2-autologous- virus multiclade panel, VRC26.07 neutralization breadth was 13%, potency of 5.0 µg/ml median IC50.
Doria-Rose2016
(antibody generation, neutralization, antibody sequence, antibody lineage)
-
VRC26.07: An atomic-level understanding of V1V2-directed bNAb recognition in a donor was used in the design of V1V2 scaffolds capable of interacting with quaternary-specific V1V2-directed bNAbs. The cocrystal structure of V1V2 with antibody CH03 from a second donor is reported and Env interactions of antibody CAP256-VRC26 from a third donor are modeled. V1V2-directed bNAbs used strand-strand interactions between a protruding Ab loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. CAP256-VRC26.07 did not bind to the monomeric V1V2 scaffolds. The quaternary dependence might be one possible explanation for this lack of recognition.
Gorman2016
(glycosylation, structure, antibody lineage)
-
CAP256-VRC26.07: 12 somatically related nAbs were isolated from donor CAP256. All nAbs of CAP256-VRC26 lineage had long CDRH3 regions necessary to penetrate the glycan shield and engage the V1V2 epitope. All 12 Abs neutralized the superinfecting virus and, with the exception of CAP256-VRC26.06, did not neutralize the primary infecting virus. In the early superinfecting virus-like sequences, K169I rare escape mutation rendered resistance against the earliest antibody CAP256-VRC26.01, followed by maturation of the lineage to tolerate K169I. Later nAbs (CAP256-VRC26.02-12) neutralized superinfecting-like viruses until escape occurred in positions 166 or 169.
Doria-Rose2014
(antibody binding site, antibody generation, glycosylation, superinfection, escape, structure)
References
Showing 7 of
7 references.
Isolation Paper
Doria-Rose2014
Nicole A. Doria-Rose, Chaim A. Schramm, Jason Gorman, Penny L. Moore, Jinal N. Bhiman, Brandon J. DeKosky, Michael J. Ernandes, Ivelin S. Georgiev, Helen J. Kim, Marie Pancera, Ryan P. Staupe, Han R. Altae-Tran, Robert T. Bailer, Ema T. Crooks, Albert Cupo, Aliaksandr Druz, Nigel J. Garrett, Kam H. Hoi, Rui Kong, Mark K. Louder, Nancy S. Longo, Krisha McKee, Molati Nonyane, Sijy O'Dell, Ryan S. Roark, Rebecca S. Rudicell, Stephen D. Schmidt, Daniel J. Sheward, Cinque Soto, Constantinos Kurt Wibmer, Yongping Yang, Zhenhai Zhang, NISC Comparative Sequencing Program, James C. Mullikin, James M. Binley, Rogier W. Sanders, Ian A. Wilson, John P. Moore, Andrew B. Ward, George Georgiou, Carolyn Williamson, Salim S. Abdool Karim, Lynn Morris, Peter D. Kwong, Lawrence Shapiro, and John R. Mascola. Developmental Pathway for Potent V1V2-Directed HIV-Neutralizing Antibodies. Nature, 509(7498):55-62, 1 May 2014. PubMed ID: 24590074.
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Bhiman2015
Jinal N. Bhiman, Colin Anthony, Nicole A. Doria-Rose, Owen Karimanzira, Chaim A. Schramm, Thandeka Khoza, Dale Kitchin, Gordon Botha, Jason Gorman, Nigel J. Garrett, Salim S. Abdool Karim, Lawrence Shapiro, Carolyn Williamson, Peter D. Kwong, John R. Mascola, Lynn Morris, and Penny L. Moore. Viral Variants That Initiate and Drive Maturation of V1V2-Directed HIV-1 Broadly Neutralizing Antibodies. Nat. Med., 21(11):1332-1336, Nov 2015. PubMed ID: 26457756.
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Doria-Rose2016
Nicole A. Doria-Rose, Jinal N. Bhiman, Ryan S. Roark, Chaim A. Schramm, Jason Gorman, Gwo-Yu Chuang, Marie Pancera, Evan M. Cale, Michael J. Ernandes, Mark K. Louder, Mangaiarkarasi Asokan, Robert T. Bailer, Aliaksandr Druz, Isabella R. Fraschilla, Nigel J. Garrett, Marissa Jarosinski, Rebecca M. Lynch, Krisha McKee, Sijy O'Dell, Amarendra Pegu, Stephen D. Schmidt, Ryan P. Staupe, Matthew S. Sutton, Keyun Wang, Constantinos Kurt Wibmer, Barton F. Haynes, Salim Abdool-Karim, Lawrence Shapiro, Peter D. Kwong, Penny L. Moore, Lynn Morris, and John R. Mascola. New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency. J. Virol., 90(1):76-91, 14 Oct 2015. PubMed ID: 26468542.
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Gorman2016
Jason Gorman, Cinque Soto, Max M. Yang, Thaddeus M. Davenport, Miklos Guttman, Robert T. Bailer, Michael Chambers, Gwo-Yu Chuang, Brandon J. DeKosky, Nicole A. Doria-Rose, Aliaksandr Druz, Michael J. Ernandes, Ivelin S. Georgiev, Marissa C. Jarosinski, M. Gordon Joyce, Thomas M. Lemmin, Sherman Leung, Mark K. Louder, Jonathan R. McDaniel, Sandeep Narpala, Marie Pancera, Jonathan Stuckey, Xueling Wu, Yongping Yang, Baoshan Zhang, Tongqing Zhou, NISC Comparative Sequencing Program, James C. Mullikin, Ulrich Baxa, George Georgiou, Adrian B. McDermott, Mattia Bonsignori, Barton F. Haynes, Penny L. Moore, Lynn Morris, Kelly K. Lee, Lawrence Shapiro, John R. Mascola, and Peter D. Kwong. Structures of HIV-1 Env V1V2 with Broadly Neutralizing Antibodies Reveal Commonalities That Enable Vaccine Design. Nat. Struct. Mol. Biol., 23(1):81-90, Jan 2016. PubMed ID: 26689967.
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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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Johnson2018
Erik L. Johnson, Nicole A. Doria-Rose, Jason Gorman, Jinal N. Bhiman, Chaim A. Schramm, Ashley Q. Vu, William H. Law, Baoshan Zhang, Valerie Bekker, Salim S. Abdool Karim, Gregory C. Ippolito, Lynn Morris, Penny L. Moore, Peter D. Kwong, John R. Mascola, and George Georgiou. Sequencing HIV-Neutralizing Antibody Exons and Introns Reveals Detailed Aspects of Lineage Maturation. Nat. Commun., 9(1):4136, 8 Oct 2018. PubMed ID: 30297708.
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Reh2018
Lucia Reh, Carsten Magnus, Claus Kadelka, Denise Kühnert, Therese Uhr, Jacqueline Weber, Lynn Morris, Penny L. Moore, and Alexandra Trkola. Phenotypic Deficits in the HIV-1 Envelope Are Associated with the maturation of a V2-directed broadly neutralizing antibody lineage. PLoS Pathog., 14(1):e1006825, Jan 2018. PubMed ID: 29370298.
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