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Publication Abstract from PubMed

Elicitation of broadly neutralizing antibodies remains a long-standing goal of HIV vaccine research. Although such antibodies can arise during HIV-1 infection, gaps in our knowledge of their germline, pre-immune precursor forms, as well as on their interaction with viral Env, limit our ability to elicit them through vaccination. Studies of broadly neutralizing antibodies from the VRC01-class provide insight into progenitor B cell receptors (BCRs) that could develop into this class of antibodies. Here, we employed high-throughput heavy chain variable region (VH)/light chain variable region (VL) deep sequencing, combined with biophysical, structural, and modeling antibody analyses, to interrogate circulating potential VRC01-progenitor BCRs in healthy individuals. Our study reveals that not all humans are equally predisposed to generate VRC01-class antibodies, not all predicted progenitor VRC01-expressing B cells can bind to Env, and the CDRH3 region of germline VRC01 antibodies influence their ability to recognize HIV-1. These findings will be critical to the design of optimized immunogens that should consider CDRH3 interactions.

Differences in Allelic Frequency and CDRH3 Region Limit the Engagement of HIV Env Immunogens by Putative VRC01 Neutralizing Antibody Precursors.,Yacoob C, Pancera M, Vigdorovich V, Oliver BG, Glenn JA, Feng J, Sather DN, McGuire AT, Stamatatos L Cell Rep. 2016 Nov 1;17(6):1560-1570. doi: 10.1016/j.celrep.2016.10.017. PMID:27806295^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.