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Displaying record number 3040
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MAb ID |
VRC26.03 (CAP256-VRC26.03) |
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, broad neutralizer, escape, glycosylation, mutation acquisition, neutralization, review, structure, superinfection |
Notes
Showing 9 of
9 notes.
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VRC26.03: Membrane-bound BG505-based ApexGT Env trimer vaccine candidates, which bind to inferred germline variants of bnAbs PCT64 and PG9, were developed through directed evolution and characterized. PCT64 and PG9/PG16 lineages were identified to have the highest and most consistent frequencies of precursors in 14 HIV-unexposed donors among 5 V2-apex-targeting bnAb classes which also included PGT141-145/PGDM1400-1414, CH01-CH04 and CAP256-VRC26 lineages. CAP256-VRC26 heavy chain (HC) precursors were found in only 1/14 human HIV-naive donors with a frequency of 0.003 precursors per million BCRs.
Willis2022
(antibody lineage)
-
VRC26.03: IgA and IgG bNAbs of 3 distinct B cell lineages were characterized in a viremic controller (pt7). Two lineages comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. BNAb 7-269 in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation. Immunotherapy with 7-269 in humanized mice delayed viral rebound. AD8-infected cell killing by primary human natural killer (NK) cells via ADCC was observed with all pt7 bNAbs binding strongly to target cells and expressed as IgGs, except for 7-155. BNAbs in all three lineages targeted the N332 glycan supersite. Epitope mapping showed that all pt7 IgA and IgG bNAbs target the high-mannose patch centered on the N332 glycan without interacting with the V3 loop base, which contrasts with numerous bNAbs targeting the N332 supersite. The cryo-EM structure of 7-269 in complex with BG505 SOSIP revealed an epitope mainly composed of sugar residues comprising the N332 and N295 glycans; onto which 7-269 positions itself in a structurally similar way to 2G12. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers. Other antibodies used as controls included 10-188, 3BNC117, PGT121, PGT135, 10-1074, BG8, BG18, and SF12. Structural comparisons were made with mAbs 438-B11, CAP256-VRC26.03 and 45-VRC01.H5.F-117225.
Lorin2022
(structure)
-
VRC26.03: 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-VRC26.03: 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-VRC26.03, a potent ‘PG9-class’ bNAb. Antigenic region V2 apex (Table:1).
Walker2018
(antibody binding site, review, broad neutralizer)
-
VRC26.03: Somatic hypermutation and affinity maturation improve an antibody's complementarity with its target epitope. Mass spectroscopy and X-ray structures were used to examine two classes of mAbs, CD4 binding Abs (VRC03, VRC-PG04) and V2 binding Abs (VRC26.01, VRC26.03, VRC26.10, PG16, CH03), to determine how specific mutations that occurred during maturation affected the binding of the mAbs to their target epitope.
Davenport2016
(structure, antibody lineage)
-
VRC26.03: 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-VRC26.03 neutralized superinfecting virus and all mutants K169R/Q/I/T at <1µg/ml, and the R166K mutant at <50µg/ml. It had a neutralization breadth of ˜20%.
Bhiman2015
(escape, antibody lineage)
-
VRC26.03: 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, VRC26.03 neutralization breadth was 35%, potency of 0.061 µg/ml median IC50.
Doria-Rose2016
(antibody generation, neutralization, antibody sequence, antibody lineage)
-
VRC26.03: 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-VRC26.03 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-VRC26.03: The developmental pathway and molecular characteristics of V1V2 targeting bnAbs has been described. Twelve somatically related nAbs were isolated from donor CAP256 containing tyrosine-sulphated Ag binding loop,CDRH3 and recognizing a quaternary epitope. The phylogenetic tree showed one branch leading to CAP256-VRC26.01 and the second developed into CAP256-VRC26.02-12.The details of heavy and light chains of unmutated common ancestors are described in Fig 3. All 12 Abs except CAP256-VRC26.06 neutralized the super infecting virus. Removal of cysteine residues in CAP256-VRC26.03 resulted in loss of neutralization potency.
Doria-Rose2014
(antibody binding site, antibody generation, glycosylation, superinfection, escape, structure)
References
Showing 9 of
9 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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Davenport2016
Thaddeus M. Davenport, Jason Gorman, M. Gordon Joyce, Tongqing Zhou, Cinque Soto, Miklos Guttman, Stephanie Moquin, Yongping Yang, Baoshan Zhang, Nicole A. Doria-Rose, Shiu-Lok Hu, John R. Mascola, Peter D. Kwong, and Kelly K. Lee. Somatic Hypermutation-Induced Changes in the Structure and Dynamics of HIV-1 Broadly Neutralizing Antibodies. Structure, 20 Jul 2016. PubMed ID: 27477385.
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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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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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Lorin2022
Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebik, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, and Hugo Mouquet. Epitope Convergence of Broadly HIV-1 Neutralizing IgA and IgG Antibody Lineages in a Viremic Controller. J. Exp. Med., 219(3), 7 Mar 2022. PubMed ID: 35230385.
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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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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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