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J Exp Med. 2018 Jun 4;215(6):1589-1608. doi: 10.1084/jem.20180246. Epub 2018 May 24.

Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity.

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
University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
4
Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland.
5
Division of Infectious Diseases, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
6
Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland.
7
Division of Infectious Diseases, University Hospital of Basel, Basel, Switzerland.
8
Department of Infectious Diseases, University Hospital of Bern, Bern, Switzerland.
9
Laboratory of Virology, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland.
10
Division of Immunology and Allergy, University Hospital Lausanne, Lausanne, Switzerland.
11
Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.
12
Institute of Medical Virology, University of Zurich, Zurich, Switzerland roger.kouyos@usz.ch.
13
Institute of Medical Virology, University of Zurich, Zurich, Switzerland huldrych.guenthard@usz.ch.
14
Institute of Medical Virology, University of Zurich, Zurich, Switzerland trkola.alexandra@virology.uzh.ch.

Abstract

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development.

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