Determinants of HIV-1 broadly neutralizing antibody induction

Nat Med. 2016 Nov;22(11):1260-1267. doi: 10.1038/nm.4187. Epub 2016 Sep 26.

Abstract

Broadly neutralizing antibodies (bnAbs) are a focal component of HIV-1 vaccine design, yet basic aspects of their induction remain poorly understood. Here we report on viral, host and disease factors that steer bnAb evolution using the results of a systematic survey in 4,484 HIV-1-infected individuals that identified 239 bnAb inducers. We show that three parameters that reflect the exposure to antigen-viral load, length of untreated infection and viral diversity-independently drive bnAb evolution. Notably, black participants showed significantly (P = 0.0086-0.038) higher rates of bnAb induction than white participants. Neutralization fingerprint analysis, which was used to delineate plasma specificity, identified strong virus subtype dependencies, with higher frequencies of CD4-binding-site bnAbs in infection with subtype B viruses (P = 0.02) and higher frequencies of V2-glycan-specific bnAbs in infection with non-subtype B viruses (P = 1 × 10-5). Thus, key host, disease and viral determinants, including subtype-specific envelope features that determine bnAb specificity, remain to be unraveled and harnessed for bnAb-based vaccine design.

Publication types

  • Observational Study

MeSH terms

  • AIDS Vaccines
  • Antibodies, Neutralizing / immunology*
  • Black People*
  • CD4 Antigens / immunology
  • Drug Discovery
  • Female
  • Genetic Variation
  • HIV Antibodies / immunology*
  • HIV Infections / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Linear Models
  • Longitudinal Studies
  • Male
  • Multivariate Analysis
  • Polysaccharides / immunology
  • Prospective Studies
  • RNA, Viral / blood
  • Switzerland
  • Time Factors
  • Viral Load*
  • White People*

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • CD4 Antigens
  • HIV Antibodies
  • Polysaccharides
  • RNA, Viral