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

Tongqing Zhou, Jiang Zhu, Xueling Wu, Stephanie Moquin, Baoshan Zhang, Priyamvada Acharya, Ivelin S. Georgiev, HanR Altae-Tran, Gwo Yu Chuang, M. Gordon Joyce, Young DoKwon, Nancy S. Longo, MarkK Louder, Timothy Luongo, Krisha McKee, Chaim A. Schramm, Jeff Skinner, Yongping Yang, Zhongjia Yang, Zhenhai ZhangAnqi Zheng, Mattia Bonsignori, Barton F. Haynes, Johannes F. Scheid, Michel C. Nussenzweig, Melissa Simek, Dennis R. Burton, WayneC Koff, James C. Mullikin, Mark Connors, Lawrence Shapiro, Gary J. Nabel, John R. Mascola, Peter D. Kwong

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)245-258
Number of pages14
JournalImmunity
Volume39
Issue number2
DOIs
StatePublished - Aug 22 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Zhou, T., Zhu, J., Wu, X., Moquin, S., Zhang, B., Acharya, P., Georgiev, I. S., Altae-Tran, H., Chuang, G. Y., Joyce, M. G., DoKwon, Y., Longo, N. S., Louder, M., Luongo, T., McKee, K., Schramm, C. A., Skinner, J., Yang, Y., Yang, Z., ... Kwong, P. D. (2013). Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity, 39(2), 245-258. https://doi.org/10.1016/j.immuni.2013.04.012