Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.

Alam, S Munir; Aussedat, Baptiste; Vohra, Yusuf; Meyerhoff, R Ryan; Cale, Evan M; Walkowicz, William E; Radakovich, Nathan A; Anasti, Kara et al. · Sci Transl Med · 2017

basic_science · Level V

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Abstract

A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man<sub>9</sub>-V3). V3-glycan bnAbs bound to Man<sub>9</sub>-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man<sub>9</sub>-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man<sub>9</sub>-V3 induced V3-glycan-targeted antibodies. Thus, the Man<sub>9</sub>-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.

Medical subject headings