Determinants of HIV-1 broadly neutralizing antibody induction

Publication

Determinants of HIV-1 broadly neutralizing antibody induction

Journal Paper/Review - Sep 26, 2016

Rusert Peter, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, Fellay Jacques, Regoes Roland R, Günthard Huldrych F, Trkola Alexandra, Cavassini Matthias, Kuster Herbert, 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

Citation

Rusert P, Bernasconi E, Hoffmann M, Calmy A, Battegay M, Rauch A, Yerly S, Aubert V, Klimkait T, Böni J, Fellay J, Regoes R, Günthard H, Trkola A, Cavassini M, Kuster H, Kouyos R, Kadelka C, Ebner H, Schanz M, Huber M, Braun D, Hozé N, Scherrer A, Magnus C, Weber J, Uhr T, Cippa V, Thorball C. Determinants of HIV-1 broadly neutralizing antibody induction. Nat Med 2016

Type

Journal Paper/Review (English)

Journal

Nat Med 2016

Publication Date

Sep 26, 2016

Issn Electronic

1546-170X

Brief description/objective

UNASSIGNED
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.