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

T Zhou, J Zhu, X Wu, S Moquin, B Zhang, P Acharya… - Immunity, 2013 - cell.com
T Zhou, J Zhu, X Wu, S Moquin, B Zhang, P Acharya, IS Georgiev, HR Altae-Tran
Immunity, 2013cell.com
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 …
Summary
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 >1012 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.
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