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Determinants of HIV-1 broadly neutralizing antibody induction.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Rusert Peter, Kouyos Roger D, Kadelka Claus, Ebner Hanna, Schanz Merle, Huber Michael, Braun Dominique L, Hozé Nathanael, Scherrer Alexandra, Magnus Carsten, Weber Jacqueline, Uhr Therese, Cippa Valentina, Thorball Christian W, Kuster Herbert, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg,
Project The role of humoral immunity in HIV infection - Understanding broadly neutralizing antibody evolution
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Original article (peer-reviewed)

Journal Nature medicine
Volume (Issue) 22(11)
Page(s) 1260 - 1267
Title of proceedings Nature medicine
DOI 10.1038/nm.4187

Abstract

Broadly neutralizing antibodies (bnAbs) are a focal component of HIV-1 vaccine design, yet basic aspects of their induction remain poorly understood. Here we report on viral, host and disease factors that steer bnAb evolution using the results of a systematic survey in 4,484 HIV-1-infected individuals that identified 239 bnAb inducers. We show that three parameters that reflect the exposure to antigen-viral load, length of untreated infection and viral diversity-independently drive bnAb evolution. Notably, black participants showed significantly (P = 0.0086-0.038) higher rates of bnAb induction than white participants. Neutralization fingerprint analysis, which was used to delineate plasma specificity, identified strong virus subtype dependencies, with higher frequencies of CD4-binding-site bnAbs in infection with subtype B viruses (P = 0.02) and higher frequencies of V2-glycan-specific bnAbs in infection with non-subtype B viruses (P = 1 × 10(-5)). Thus, key host, disease and viral determinants, including subtype-specific envelope features that determine bnAb specificity, remain to be unraveled and harnessed for bnAb-based vaccine design.
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