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

Claus Kadelka, Thomas Liechti, Hanna Ebner, Merle Schanz, Peter Rusert, Nikolas Friedrich, Emanuel Stiegeler, Dominique L Braun, Michael Huber, Alexandra U Scherrer, Jacqueline Weber, Therese Uhr, Herbert Kuster, Benjamin Misselwitz, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola & Swiss HIV Cohort Study

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.
   
citation 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, Swiss HIV Cohort Study . Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity. J Exp Med 2018; 215:1589-1608.
   
type journal paper/review (English)
date of publishing 24-05-2018
journal title J Exp Med (215/6)
ISSN electronic 1540-9538
pages 1589-1608
PubMed 29794117
DOI 10.1084/jem.20180246