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Scientific Article
unige:98817 
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Determinants of HIV-1 broadly neutralizing antibody induction |
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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 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 | |
| Identifiers | DOI: 10.1038/nm.4187 PMID: 27668936 | |
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| Research groups | Groupe Laurent Kaiser (virologie clinique) (668) VIH/SIDA (930) | |
| 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 https://archive-ouverte.unige.ch/unige:98817 |
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