Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Roger D. Kouyos (), Peter Rusert, Claus Kadelka, Michael Huber, Alex Marzel, Hanna Ebner, Merle Schanz, Thomas Liechti, Nikolas Friedrich, Dominique L. Braun, Alexandra U. Scherrer, Jacqueline Weber, Therese Uhr, Nicolas S. Baumann, Christine Leemann, Herbert Kuster, Jean-Philippe Chave, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Karin J. Metzner, Huldrych F. Günthard () and Alexandra Trkola ()
Additional contact information
Roger D. Kouyos: University of Zurich
Peter Rusert: University of Zurich
Claus Kadelka: University of Zurich
Michael Huber: University of Zurich
Alex Marzel: University of Zurich
Hanna Ebner: University of Zurich
Merle Schanz: University of Zurich
Thomas Liechti: University of Zurich
Nikolas Friedrich: University of Zurich
Dominique L. Braun: University of Zurich
Alexandra U. Scherrer: University of Zurich
Jacqueline Weber: University of Zurich
Therese Uhr: University of Zurich
Nicolas S. Baumann: University of Zurich
Christine Leemann: University of Zurich
Herbert Kuster: University of Zurich
Jean-Philippe Chave: Clinique de La Source
Matthias Cavassini: University of Lausanne
Enos Bernasconi: Regional Hospital Lugano
Matthias Hoffmann: Cantonal Hospital St. Gallen
Alexandra Calmy: University of Geneva
Manuel Battegay: University of Basel
Andri Rauch: University of Bern
Sabine Yerly: University of Geneva
Vincent Aubert: University of Lausanne
Thomas Klimkait: University of Basel
Jürg Böni: University of Zurich
Karin J. Metzner: University of Zurich
Huldrych F. Günthard: University of Zurich
Alexandra Trkola: University of Zurich

Nature, 2018, vol. 561, issue 7723, 406-410

Abstract: 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.

Keywords: Transmission Pairs; Partner Transmission; bNAb Responses; Neutralization Strength; Lenge Infection (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0517-0

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