Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Publication

Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Journal Paper/Review - Sep 10, 2018

Kouyos Roger D, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, Metzner Karin J, Günthard Huldrych F, Trkola Alexandra, Chave Jean-Philippe, Kuster Herbert, Leemann Christine, 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, Swiss HIV Cohort Study

Citation

Kouyos R, Cavassini M, Bernasconi E, Hoffmann M, Calmy A, Battegay M, Rauch A, Yerly S, Aubert V, Klimkait T, Böni J, Metzner K, Günthard H, Trkola A, Chave J, Kuster H, Leemann C, Rusert P, Kadelka C, Huber M, Marzel A, Ebner H, Schanz M, Liechti T, Friedrich N, Braun D, Scherrer A, Weber J, Uhr T, Baumann N, Swiss HIV Cohort Study. Tracing HIV-1 strains that imprint broadly neutralizing antibody responses. Nature 2018; 561:406-410.

Type

Journal Paper/Review (English)

Journal

Nature 2018; 561

Publication Date

Sep 10, 2018

Issn Electronic

1476-4687

Pages

406-410

Brief description/objective

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.