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

Publication

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

Journal Paper/Review - May 24, 2018

Kadelka Claus, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, Kouyos Roger D, Günthard Huldrych F, Trkola Alexandra, Cavassini Matthias, Misselwitz Benjamin, 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, Swiss HIV Cohort Study

Citation

Kadelka C, Bernasconi E, Hoffmann M, Calmy A, Battegay M, Rauch A, Yerly S, Aubert V, Klimkait T, Böni J, Kouyos R, Günthard H, Trkola A, Cavassini M, Misselwitz B, Liechti T, Ebner H, Schanz M, Rusert P, Friedrich N, Stiegeler E, Braun D, Huber M, Scherrer A, Weber J, Uhr T, Kuster H, 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)

Journal

J Exp Med 2018; 215

Publication Date

May 24, 2018

Issn Electronic

1540-9538

Pages

1589-1608

Brief description/objective

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.