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

Determinants of HIV-1 broadly neutralizing antibody induction.

Author information

1
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
2
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
3
Institute of Integrative Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
4
Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
5
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
6
University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
7
Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland.
8
Division of Infectious Diseases, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
9
Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.
10
Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland.
11
Department of Infectious Diseases, Inselspital, Bern University Hospital, Bern, Switzerland.
12
Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland.
13
Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland.
14
Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.

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.

PMID:
27668936
DOI:
10.1038/nm.4187
[Indexed for MEDLINE]

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