Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity
| Autor: | 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 D, Günthard, Huldrych F, Trkola, Alexandra, Swiss HIV Cohort Study |
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| Přispěvatelé: | Swiss HIV Cohort Study, University of Zurich, Trkola, Alexandra |
| Rok vydání: | 2018 |
| Předmět: |
10028 Institute of Medical Virology
0301 basic medicine Antibody Formation/immunology Human immunodeficiency virus (HIV) HIV Infections Disease HIV Antibodies medicine.disease_cause gag Gene Products Human Immunodeficiency Virus Neutralization 10234 Clinic for Infectious Diseases HIV Infections/immunology Env Gene Products 0302 clinical medicine HIV-1/immunology Immunology and Allergy 030212 general & internal medicine Immunoglobulin G/immunology Research Articles African Continental Ancestry Group ddc:616 Gag Gene Products biology Human Immunodeficiency Virus/immunology Antibodies Neutralizing/immunology Chronic Disease Demography HIV Antibodies/immunology Humans Protein Binding Viral Load env Gene Products Human Immunodeficiency Virus/immunology gag Gene Products Human Immunodeficiency Virus/immunology env Gene Products Human Immunodeficiency Virus virus diseases Antigen binding 3. Good health 10219 Clinic for Gastroenterology and Hepatology 2723 Immunology and Allergy Antibody Viral load Immunology Black People 610 Medicine & health Antibodies Article 03 medical and health sciences Antigen medicine 2403 Immunology Antibodies Neutralizing Neutralizing/immunology 030104 developmental biology Antibody response Immunoglobulin G Antibody Formation biology.protein HIV-1 |
| Zdroj: | The Journal of Experimental Medicine The Journal of experimental medicine, vol. 215, no. 6, pp. 1589-1608 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 The Journal of experimental medicine, Vol. 215, No 6 (2018) pp. 1589-1608 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20180246 |
| Popis: | Kadelka et al. show that parameters linked with HIV-1 broadly neutralizing antibody (bnAb) development shape HIV-1–binding antibody responses in an antigen and IgG subclass dependent manner. Identified HIV-1 antibody signature landscapes reveal a shift toward IgG1-driven responses in bnAb developers. 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. |
| Databáze: | OpenAIRE |
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