Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.
Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.
Saunders, KO; Nicely, NI; Wiehe, K; Bonsignori, M; Meyerhoff, RR; Parks, R; Walkowicz, WE; Aussedat, B; Wu, NR; Cai, F; Vohra, Y; Park, PK; Eaton, A; Go, EP; Sutherland, LL; Scearce, RM; Barouch, DH; Zhang, R; Von Holle, T; Overman, RG; Anasti, K; Sanders, RW; Moody, MA; Kepler, TB; Korber, B; Desaire, H; Santra, S; Letvin, NL; Nabel, GJ; Montefiori, DC; Tomaras, GD; Liao, H-X; Alam, SM; Danishefsky, SJ; Haynes, BF
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