Immunization expands HIV-1 V3-glycan specific B-cells in mice and macaques

Broadly neutralizing monoclonal antibodies protect against HIV-1 infection in animal models, suggesting that a vaccine that elicits them in humans would be effective. However, it has not yet been possible to elicit adequate serologic responses by vaccination. To activate B-cells expressing precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed a new immunogen, RC1, which facilitates recognition of the V3-glycan patch on HIV-1 envelope while concealing non-conserved immunodominant regions by addition of glycans and/or multimerization on virus-like particles. Mouse, rabbit and rhesus macaque immunizations with RC1 elicited serologic responses targeting the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that RC1 immunization expands clones of B-cells carrying anti-V3-glycan patch antibodies that resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies to elicit V3-glycan antibodies in the context of polyclonal repertoires.