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Title

Determinants of HIV-1 broadly neutralizing antibody induction

Authors
Rusert, Peter
Kouyos, Roger D
Kadelka, Claus
Ebner, Hanna
Schanz, Merle
Huber, Michael
Braun, Dominique L
Hozé, Nathanael
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Published in Nature medicine. 2016, vol. 22, no. 11, p. 1260-1267
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 VaccinesAfrican Continental Ancestry GroupAntibodiesNeutralizing/immunologyAntigensCD4/immunologyDrug DiscoveryEuropean Continental Ancestry GroupFemaleGenetic VariationHIV Antibodies/immunologyHIV Infections/immunologyHIV-1/genetics/immunologyHumansLinear ModelsLongitudinal StudiesMaleMultivariate AnalysisPolysaccharides/immunologyProspective StudiesRNAViral/bloodSwitzerlandTime FactorsViral Load
Identifiers
PMID: 27668936
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Article (Published version) (1.2 MB) - public document Free access
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Research groups Groupe Laurent Kaiser (virologie clinique) (668)
VIH/SIDA (930)
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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 https://archive-ouverte.unige.ch/unige:98817

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Deposited on : 2017-11-09

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