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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author 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, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, Kouyos Roger, GünthardHuldrych, TrkolaAlexandra, the Swiss HIV Cohort,
Project Understanding HIV-1 broadly neutralizing antibody evolution - The Swiss 4.5K Screen
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Original article (peer-reviewed)

Journal The Journal of Experimental Medicine
Volume (Issue) 215(6)
Page(s) 1589 - 1608
Title of proceedings The Journal of Experimental Medicine
DOI 10.1084/jem.20180246

Open Access

URL http://doi.org/10.1084/jem.20180246
Type of Open Access Publisher (Gold Open Access)

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.
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