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

Nature. 2019 Jun;570(7762):468-473. doi: 10.1038/s41586-019-1250-z. Epub 2019 May 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / ultrastructure
  • Antibody Affinity
  • Antibody Specificity / immunology
  • Antigen-Antibody Complex / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Clone Cells / cytology
  • Clone Cells / immunology*
  • Cloning, Molecular
  • Cross-Priming / immunology
  • Cryoelectron Microscopy
  • Female
  • HIV Antibodies / chemistry
  • HIV Antibodies / genetics
  • HIV Antibodies / immunology
  • HIV Antibodies / ultrastructure
  • HIV-1 / chemistry*
  • HIV-1 / immunology*
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / ultrastructure
  • Lymphocyte Activation
  • Macaca mulatta / immunology*
  • Male
  • Mice
  • Models, Molecular
  • Polysaccharides / immunology
  • Rabbits
  • Somatic Hypermutation, Immunoglobulin
  • Vaccination*


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Antigen-Antibody Complex
  • HIV Antibodies
  • Immunodominant Epitopes
  • Polysaccharides