Determinants of HIV-1 broadly neutralizing antibody induction

Rusert, P. and Kouyos, R. D. and Kadelka, C. and Ebner, H. and Schanz, M. and Huber, M. and Braun, D. L. and Hoze, N. and Scherrer, A. and Magnus, C. and Weber, J. and Uhr, T. and Cippa, V. and Thorball, C. W. and Kuster, H. and Cavassini, M. and Bernasconi, E. and Hoffmann, M. and Calmy, A. and Battegay, M. and Rauch, A. and Yerly, S. and Aubert, V. and Klimkait, T. and Boni, J. and Fellay, J. and Regoes, R. R. and Gunthard, H. F. and Trkola, A. and Swiss, H. I. V. Cohort Study. (2016) Determinants of HIV-1 broadly neutralizing antibody induction. Nat Med, 22 (11). pp. 1260-1267.

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Official URL: https://edoc.unibas.ch/62180/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1546-170X (Electronic) 1078-8956 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 May 2020 09:40
Deposited On:26 May 2020 09:40

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