Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques

Abstract

BG505 SOSIP.664 is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential immunogen regime for an HIV vaccine. BG505 has been tested in many preclinical animal models and is now in first-in-human phase I clinical trials. Rhesus macaques are considered the most similar in terms of nAb responses to humans. Accordingly, we report here the isolation of 45 BG505 nAbs with multiple specificities from immunized and infected rhesus macaques.Notably, all of the autologous nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. Finally, we identify a “public clonotype” that targets the immunodominant C3/V5 epitope, which suggests that such common rearrangements might greatly influence immunodominant humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP.664 trimer in human clinical trials.