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Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies.


ABSTRACT: Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.

SUBMITTER: Zhou T 

PROVIDER: S-EPMC3985390 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies.

Zhou Tongqing T   Zhu Jiang J   Wu Xueling X   Moquin Stephanie S   Zhang Baoshan B   Acharya Priyamvada P   Georgiev Ivelin S IS   Altae-Tran Han R HR   Chuang Gwo-Yu GY   Joyce M Gordon MG   Kwon Young Do YD   Longo Nancy S NS   Louder Mark K MK   Luongo Timothy T   McKee Krisha K   Schramm Chaim A CA   Skinner Jeff J   Yang Yongping Y   Yang Zhongjia Z   Zhang Zhenhai Z   Zheng Anqi A   Bonsignori Mattia M   Haynes Barton F BF   Scheid Johannes F JF   Nussenzweig Michel C MC   Simek Melissa M   Burton Dennis R DR   Koff Wayne C WC   Mullikin James C JC   Connors Mark M   Shapiro Lawrence L   Nabel Gary J GJ   Mascola John R JR   Kwong Peter D PD  

Immunity 20130801 2


Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC  ...[more]

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