Vaccination induces HIV broadly neutralizing antibody precursors in humans

Science. 2022 Dec 2;378(6623):eadd6502. doi: 10.1126/science.add6502. Epub 2022 Dec 2.


Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines* / immunology
  • Adjuvants, Immunologic
  • Adult
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies* / genetics
  • Broadly Neutralizing Antibodies* / immunology
  • Female
  • Germ Cells* / immunology
  • HIV Antibodies* / genetics
  • HIV Antibodies* / immunology
  • HIV Infections* / prevention & control
  • Humans
  • Immunoglobulin Heavy Chains* / genetics
  • Immunoglobulin Heavy Chains* / immunology
  • Immunoglobulin Light Chains* / genetics
  • Immunoglobulin Light Chains* / immunology
  • Male
  • Mutation
  • Vaccination


  • Adjuvants, Immunologic
  • AIDS Vaccines
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • Immunoglobulin Light Chains
  • Immunoglobulin Heavy Chains