- Escolano, Amelia;
- Gristick, Harry B;
- Abernathy, Morgan E;
- Merkenschlager, Julia;
- Gautam, Rajeev;
- Oliveira, Thiago Y;
- Pai, Joy;
- West, Anthony P;
- Barnes, Christopher O;
- Cohen, Alexander A;
- Wang, Haoqing;
- Golijanin, Jovana;
- Yost, Daniel;
- Keeffe, Jennifer R;
- Wang, Zijun;
- Zhao, Peng;
- Yao, Kai-Hui;
- Bauer, Jens;
- Nogueira, Lilian;
- Gao, Han;
- Voll, Alisa V;
- Montefiori, David C;
- Seaman, Michael S;
- Gazumyan, Anna;
- Silva, Murillo;
- McGuire, Andrew T;
- Stamatatos, Leonidas;
- Irvine, Darrell J;
- Wells, Lance;
- Martin, Malcolm A;
- Bjorkman, Pamela J;
- Nussenzweig, Michel C
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.