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

Article

关键词: BROADLY NEUTRALIZING ANTIBODIES;    ENVELOPE GLYCOPROTEIN;    AFFINITY;    VACCINE;    RECOGNITION;    TARGET;    IDENTIFICATION;    VULNERABILITY;    VALIDATION;    SUPERSITE;   

DOI  :  10.1038/s41586-019-1250-z

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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