Cell Reports
Volume 32, Issue 10, 8 September 2020, 108122
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Article
Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques

https://doi.org/10.1016/j.celrep.2020.108122Get rights and content
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Highlights

  • SHIV-infected and SOSIP-immunized macaques elicit similar neutralizing antibodies

  • Four neutralizing epitope specificities are found in BG505 SOSIP-immunized macaques

  • Antibodies to V1/V3 and C3/V5 are potently neutralizing and contribute to protection

  • Public clonotype is identified against immunodominant C3/V5 epitope

Summary

BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a “public clonotype” that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.

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