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

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Version: Final published version
License: CC BY-NC-SA 4.0
Serval ID
serval:BIB_6F22C97F0906
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity.
Journal
The Journal of experimental medicine
Author(s)
Kadelka C., Liechti T., Ebner H., Schanz M., Rusert P., Friedrich N., Stiegeler E., Braun D.L., Huber M., Scherrer A.U., Weber J., Uhr T., Kuster H., Misselwitz B., Cavassini M., Bernasconi E., Hoffmann M., Calmy A., Battegay M., Rauch A., Yerly S., Aubert V., Klimkait T., Böni J., Kouyos R.D., Günthard H.F., Trkola A.
Working group(s)
Swiss HIV Cohort Study
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
04/06/2018
Peer-reviewed
Oui
Volume
215
Number
6
Pages
1589-1608
Language
english
Notes
Publication types: Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
African Continental Ancestry Group, Antibodies, Neutralizing/immunology, Antibody Formation/immunology, Chronic Disease, Demography, HIV Antibodies/immunology, HIV Infections/immunology, HIV-1/immunology, Humans, Immunoglobulin G/immunology, Protein Binding, Viral Load, env Gene Products, Human Immunodeficiency Virus/immunology, gag Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
31/05/2018 19:03
Last modification date
20/08/2019 15:28
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