Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.

TitleDevelopmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Publication TypeJournal Article
Year of Publication2014
AuthorsDoria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, Dekosky BJ, Ernandes MJ, Georgiev IS, Kim HJ, Pancera M, Staupe RP, Altae-Tran HR, Bailer RT, Crooks ET, Cupo A, Druz A, Garrett NJ, Hoi KH, Kong R, Louder MK, Longo NS, McKee K, Nonyane M, O'Dell S, Roark RS, Rudicell RS, Schmidt SD, Sheward DJ, Soto C, Wibmer CKurt, Yang Y, Zhang Z, Mullikin JC, Binley JM, Sanders RW, Wilson IA, Moore JP, Ward AB, Georgiou G, Williamson C, Karim SSAbdool, Morris L, Kwong PD, Shapiro L, Mascola JR
JournalNature
Volume509
Issue7498
Start Page55
Pagination55-62
Date Published05/01/2014
ISSN1476-4687
Abstract

Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.

DOI10.1038/nature13036
Alternate JournalNature
PubMed ID24590074
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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