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
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abstract
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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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citation
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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.
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type
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journal paper/review (English)
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date of publishing
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10-09-2018
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journal title
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Nature (561/7723)
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ISSN electronic
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1476-4687
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pages
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406-410
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PubMed
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30202088
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DOI
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10.1038/s41586-018-0517-0
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