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Scientific article
Open access
English

Determinants of HIV-1 broadly neutralizing antibody induction

Published inNature Medicine, vol. 22, no. 11, p. 1260-1267
Publication date2016
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.

Keywords
  • AIDS Vaccines
  • African Continental Ancestry Group
  • Antibodies
  • Neutralizing/immunology
  • Antigens
  • CD4/immunology
  • Drug Discovery
  • European Continental Ancestry Group
  • Female
  • Genetic Variation
  • HIV Antibodies/immunology
  • HIV Infections/immunology
  • HIV-1/genetics/immunology
  • Humans
  • Linear Models
  • Longitudinal Studies
  • Male
  • Multivariate Analysis
  • Polysaccharides/immunology
  • Prospective Studies
  • RNA
  • Viral/blood
  • Switzerland
  • Time Factors
  • Viral Load
Citation (ISO format)
RUSERT, Peter et al. Determinants of HIV-1 broadly neutralizing antibody induction. In: Nature Medicine, 2016, vol. 22, n° 11, p. 1260–1267. doi: 10.1038/nm.4187
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Article (Published version)
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ISSN of the journal1078-8956
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