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


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.

SUBMITTER: Doria-Rose NA 

PROVIDER: S-EPMC4395007 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Doria-Rose Nicole A NA   Schramm Chaim A CA   Gorman Jason J   Moore Penny L PL   Bhiman Jinal N JN   DeKosky Brandon J BJ   Ernandes Michael J MJ   Georgiev Ivelin S IS   Kim Helen J HJ   Pancera Marie M   Staupe Ryan P RP   Altae-Tran Han R HR   Bailer Robert T RT   Crooks Ema T ET   Cupo Albert A   Druz Aliaksandr A   Garrett Nigel J NJ   Hoi Kam H KH   Kong Rui R   Louder Mark K MK   Longo Nancy S NS   McKee Krisha K   Nonyane Molati M   O'Dell Sijy S   Roark Ryan S RS   Rudicell Rebecca S RS   Schmidt Stephen D SD   Sheward Daniel J DJ   Soto Cinque C   Wibmer Constantinos Kurt CK   Yang Yongping Y   Zhang Zhenhai Z   Mullikin James C JC   Binley James M JM   Sanders Rogier W RW   Wilson Ian A IA   Moore John P JP   Ward Andrew B AB   Georgiou George G   Williamson Carolyn C   Abdool Karim Salim S SS   Morris Lynn L   Kwong Peter D PD   Shapiro Lawrence L   Mascola John R JR  

Nature 20140302 7498


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))  ...[more]

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