Publikation

Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Wissenschaftlicher Artikel/Review - 10.09.2018

Bereiche
PubMed
DOI

Zitation
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.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Nature 2018; 561
Veröffentlichungsdatum
10.09.2018
eISSN (Online)
1476-4687
Seiten
406-410
Kurzbeschreibung/Zielsetzung

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.