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Nature. 2018 Sep;561(7723):406-410. doi: 10.1038/s41586-018-0517-0. Epub 2018 Sep 10.

Tracing HIV-1 strains that imprint broadly neutralizing antibody responses.

Author information

1
Institute of Medical Virology, University of Zurich, Zurich, Switzerland. roger.kouyos@usz.ch.
2
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. roger.kouyos@usz.ch.
3
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
4
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
5
ImmunoTechnology Section, Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
6
Clinique de La Source, Lausanne, Switzerland.
7
Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
8
Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
9
Division of Infectious Diseases, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
10
Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
11
Division of Infectious Diseases, University Hospital Basel, University of Basel, Basel, Switzerland.
12
Department of Infectious Diseases, University Hospital Bern, University of Bern, Bern, Switzerland.
13
Laboratory of Virology, Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
14
Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
15
Division of Infection Diagnostics, Department of Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.
16
Institute of Medical Virology, University of Zurich, Zurich, Switzerland. huldrych.guenthard@usz.ch.
17
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. huldrych.guenthard@usz.ch.
18
Institute of Medical Virology, University of Zurich, Zurich, Switzerland. trkola.alexandra@virology.uzh.ch.

Abstract

Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines1. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare2, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.

PMID:
30202088
DOI:
10.1038/s41586-018-0517-0
[Indexed for MEDLINE]

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