Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
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 (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-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 Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
Alam, SM; Aussedat, B; Vohra, Y; Meyerhoff, RR; Cale, EM; Walkowicz, WE; Radakovich, NA; Anasti, K; Armand, L; Parks, R; Sutherland, L; Scearce, R; Joyce, MG; Pancera, M; Druz, A; Georgiev, IS; Von Holle, T; Eaton, A; Fox, C; Reed, SG; Louder, M; Bailer, RT; Morris, L; Abdool-Karim, SS; Cohen, M; Liao, H-X; Montefiori, DC; Park, PK; Fernández-Tejada, A; Wiehe, K; Santra, S; Kepler, TB; Saunders, KO; Sodroski, J; Kwong, PD; Mascola, JR; Bonsignori, M; Moody, MA; Danishefsky, S; Haynes, BF
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