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

Kadelka, Claus
Liechti, Thomas
Ebner, Hanna
Schanz, Merle
Rusert, Peter
Friedrich, Nikolas
Stiegeler, Emanuel
Braun, Dominique L
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Published in The Journal of experimental medicine. 2018, vol. 215, no. 6, p. 1589-1608
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 GroupAntibodiesNeutralizing/immunologyAntibody Formation/immunologyChronic DiseaseDemographyHIV Antibodies/immunologyHIV Infections/immunologyHIV-1/immunologyHumansImmunoglobulin G/immunologyProtein BindingViral LoadEnv Gene ProductsHuman Immunodeficiency Virus/immunologyGag Gene Products
PMID: 29794117
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Research groups Groupe Laurent Kaiser (virologie clinique) (668)
VIH/SIDA (930)
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KADELKA, Claus et al. Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity. In: The Journal of experimental medicine, 2018, vol. 215, n° 6, p. 1589-1608. doi: 10.1084/jem.20180246 https://archive-ouverte.unige.ch/unige:143778

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Deposited on : 2020-10-29

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