A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses

Science. 2019 Dec 6;366(6470):eaax4380. doi: 10.1126/science.aax4380. Epub 2019 Oct 31.


Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.

Publication types

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

MeSH terms

  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology*
  • Adoptive Transfer
  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies / chemistry
  • Broadly Neutralizing Antibodies / immunology*
  • Complementarity Determining Regions / immunology
  • Directed Molecular Evolution / methods*
  • Disease Models, Animal
  • HEK293 Cells
  • HIV Antibodies / chemistry
  • HIV Antibodies / immunology*
  • Humans
  • Immunogenicity, Vaccine*
  • Mice
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / immunology
  • env Gene Products, Human Immunodeficiency Virus / genetics*
  • env Gene Products, Human Immunodeficiency Virus / immunology*


  • AIDS Vaccines
  • Broadly Neutralizing Antibodies
  • Complementarity Determining Regions
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus