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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, Alexandra Trkola & Swiss HIV Cohort Study

abstract Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare, 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.
   
citation Kouyos R D, Rusert P, Kadelka C, Huber M, Marzel A, Ebner H, Schanz M, Liechti T, Friedrich N, Braun D L, Scherrer A U, Weber J, Uhr T, Baumann N S, Leemann C, Kuster H, Chave J P, Cavassini M, Bernasconi E, Hoffmann M, Calmy A, Battegay M, Rauch A, Yerly S, Aubert V, Klimkait T, Böni J, Metzner K J, Günthard H F, Trkola A, Swiss HIV Cohort Study . Tracing HIV-1 strains that imprint broadly neutralizing antibody responses. Nature 2018; 561:406-410.
   
type journal paper/review (English)
date of publishing 10-09-2018
journal title Nature (561/7723)
ISSN electronic 1476-4687
pages 406-410
PubMed 30202088
DOI 10.1038/s41586-018-0517-0