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Priming of Multiple HIV Neutralizing B Cell Precursors in Humans
Chen-Hao Yeh1,2, Stephen R Walsh3,4, Ruth Parsons1,5
1Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, 27710, USA.
Abstract:
Induction of HIV broadly neutralizing antibodies (bnAbs) is a major vaccine goal. We evaluated in a Phase I trial the immunogenicity of a transmitted/founder (TF) envelope trimer designed to prime the heavy chain third complementarity determining region (CDRH3)-dominant class of CD4-binding site (CD4bs) HIV bnAb precursors. B cells producing neutralizing antibodies were isolated from all participants. CD4bs-directed, CDRH3-dominant candidate bnAb precursors were identified in 73% of vaccinees, including one lineage with heterologous neutralization of global HIV isolates. Structural studies elucidated the epitopes of CD4bs CDRH3-dominant, non-CD4bs V1/V3-directed, and gp120/gp41 interface-targeting neutralizing antibodies. Thus, a TF Env trimer can prime a diverse, polyclonal neutralizing B cell repertoire in humans, providing multiple B cell lineages for advancement by sequential boosting toward HIV bnAb breadth.
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