Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice

Science. 2016 Sep 30;353(6307):1557-1560. doi: 10.1126/science.aah3945. Epub 2016 Sep 8.


A major obstacle to a broadly neutralizing antibody (bnAb)-based HIV vaccine is the activation of appropriate B cell precursors. Germline-targeting immunogens must be capable of priming rare bnAb precursors in the physiological setting. We tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8 60mer (60-subunit self-assembling nanoparticle) to activate appropriate precursors in mice transgenic for human immunoglobulin (Ig) loci. Despite an average frequency of, at most, about one VRC01-class precursor per mouse, we found that at least 29% of singly immunized mice produced a VRC01-class memory response, suggesting that priming generally succeeded when at least one precursor was present. The results demonstrate the feasibility of using germline targeting to prime specific and exceedingly rare bnAb-precursor B cells within a humanlike repertoire.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Blocking / immunology
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • Broadly Neutralizing Antibodies
  • Genes, Immunoglobulin Heavy Chain / genetics
  • Genes, Immunoglobulin Heavy Chain / immunology*
  • Genetic Loci
  • Germ Cells / immunology
  • HIV Antibodies / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunization
  • Immunologic Memory
  • Mice
  • Mice, Transgenic
  • Nanoparticles
  • Precursor Cells, B-Lymphoid / immunology*
  • Protein Domains / genetics
  • Protein Domains / immunology


  • AIDS Vaccines
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • VRC01 monoclonal antibody