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Determinants of HIV-1 broadly neutralizing antibody induction
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4393089
Author(s)
Rusert, P.; Kouyos, R. D.; Kadelka, C.; Ebner, H.; Schanz, M.; Huber, M.; Braun, D. L.; Hoze, N.; Scherrer, A.; Magnus, C.; Weber, J.; Uhr, T.; Cippa, V.; Thorball, C. W.; Kuster, H.; Cavassini, M.; Bernasconi, E.; Hoffmann, M.; Calmy, A.; Battegay, M.; Rauch, A.; Yerly, S.; Aubert, V.; Klimkait, T.; Boni, J.; Fellay, J.; Regoes, R. R.; Gunthard, H. F.; Trkola, A.; Swiss, H. I. V. Cohort Study
Determinants of HIV-1 broadly neutralizing antibody induction
Journal
Nat Med
Volume
22
Number
11
Pages / Article-Number
1260-1267
Mesh terms
AIDS Vaccines; African Continental Ancestry Group; Antibodies, Neutralizing, immunology; CD4 Antigens, immunology; Drug Discovery; European Continental Ancestry Group; Female; Genetic Variation; HIV Antibodies, immunology; HIV Infections, immunology; HIV-1, immunology; Humans; Linear Models; Longitudinal Studies; Male; Multivariate Analysis; Polysaccharides, immunology; Prospective Studies; RNA, Viral, blood; Switzerland; Time Factors; Viral Load
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 x 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.
