Back
Full-text
Journal article

Determinants of HIV-1 broadly neutralizing antibody induction.

  • Rusert P Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Kouyos RD Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Kadelka C Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Ebner H Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Schanz M Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Huber M Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Braun DL Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Hozé N Institute of Integrative Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
  • Scherrer A Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Magnus C Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Weber J Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Uhr T Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Cippa V Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Thorball CW Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Kuster H Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Cavassini M University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
  • Bernasconi E Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland.
  • Hoffmann M Division of Infectious Diseases, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
  • Calmy A Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.
  • Battegay M Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland.
  • Rauch A Department of Infectious Diseases, Inselspital, Bern University Hospital, Bern, Switzerland.
  • Yerly S Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland.
  • Aubert V Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland.
  • Klimkait T Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.
  • Böni J Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Fellay J Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Regoes RR Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Günthard HF Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Trkola A Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Show more…
  • 2016-11-08
Published in:
  • Nature medicine. - 2016
AIDS Vaccines
African Continental Ancestry Group
Antibodies, Neutralizing
CD4 Antigens
Drug Discovery
European Continental Ancestry Group
Female
Genetic Variation
HIV Antibodies
HIV Infections
HIV-1
Humans
Linear Models
Longitudinal Studies
Male
Multivariate Analysis
Polysaccharides
Prospective Studies
RNA, Viral
Switzerland
Time Factors
Viral Load
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/44078
Statistics
Document views: 80 File downloads:
  • Full-text: 0