Determinants of HIV-1 broadly neutralizing antibody induction.

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; ... (2016). Determinants of HIV-1 broadly neutralizing antibody induction. Nature medicine, 22(11), pp. 1260-1267. Nature Publishing Group 10.1038/nm.4187

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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 × 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Rauch, Andri

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1078-8956

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

08 Nov 2016 10:22

Last Modified:

12 Jan 2017 01:30

Publisher DOI:

10.1038/nm.4187

PubMed ID:

27668936

BORIS DOI:

10.7892/boris.89060

URI:

https://boris.unibe.ch/id/eprint/89060

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