Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity.

Kadelka, Claus; Liechti, Thomas; Ebner, Hanna; Schanz, Merle; Rusert, Peter; Friedrich, Nikolas; Stiegeler, Emanuel; Braun, Dominique L; Huber, Michael; Scherrer, Alexandra U; Weber, Jacqueline; Uhr, Therese; Kuster, Herbert; Misselwitz, Benjamin; Cavassini, Matthias; Bernasconi, Enos; Hoffmann, Matthias; Calmy, Alexandra; Battegay, Manuel; Rauch, Andri; ... (2018). Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity. Journal of experimental medicine, 215(6), pp. 1589-1608. Rockefeller University Press 10.1084/jem.20180246

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Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1-binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass-dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development.

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:

1540-9538

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

20 Jul 2018 12:54

Last Modified:

24 Oct 2019 20:26

Publisher DOI:

10.1084/jem.20180246

PubMed ID:

29794117

BORIS DOI:

10.7892/boris.117015

URI:

https://boris.unibe.ch/id/eprint/117015

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