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

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; ... (2018). Tracing HIV-1 strains that imprint broadly neutralizing antibody responses. Nature, 561(7723), pp. 406-410. Macmillan Journals Ltd. 10.1038/s41586-018-0517-0

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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.

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