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Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Kouyos Roger D., Rusert Peter, Kadelka Claus, Huber Michael, Marzel Alex, Ebner Hanna, Schanz Merle, Liechti Thomas, Friedrich Nikolas, Braun Dominique L., Scherrer Alexandra U., Weber Jacqueline, Uhr Therese, Baumann Nicolas S., Leemann Christine, Kuster Herbert, Chave Jean-Philippe, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, KlimkaitThomas, BöniJürg, MetznerKarin, GünthardHuldrych, TrkolaAlexandra, the Swiss HIV Cohort,
Project Understanding HIV-1 broadly neutralizing antibody evolution - The Swiss 4.5K Screen
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Original article (peer-reviewed)

Journal Nature
Volume (Issue) 561(7723)
Page(s) 406 - 410
Title of proceedings Nature
DOI 10.1038/s41586-018-0517-0


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.