Immunization expands B cells specific to HIV-1 V3 glycan in mice and macaques.
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Escolano, A; Gristick, HB; Abernathy, ME; Merkenschlager, J; Gautam, R; Oliveira, TY; Pai, J; West, AP; Barnes, CO; Cohen, AA; Wang, H; Golijanin, J; Yost, D; Keeffe, JR; Wang, Z; Zhao, P; Yao, K-H; Bauer, J; Nogueira, L; Gao, H; Voll, AV; Montefiori, DC; Seaman, MS; Gazumyan, A; Silva, M; McGuire, AT; Stamatatos, L; Irvine, DJ; Wells, L; Martin, MA; Bjorkman, PJ; Nussenzweig, MC
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