Header

UZH-Logo

Maintenance Infos

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


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.

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.

Statistics

Citations

Dimensions.ai Metrics
11 citations in Web of Science®
6 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

36 downloads since deposited on 07 Jun 2018
29 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:24 May 2018
Deposited On:07 Jun 2018 06:41
Last Modified:24 Sep 2019 23:30
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20180246
PubMed ID:29794117
Project Information:
  • : FunderSNSF
  • : Grant ID33CS30_148522
  • : Project TitleSwiss HIV Cohort Study (SHCS)
  • : FunderSNSF
  • : Grant ID314730_172790
  • : Project TitleUnderstanding HIV-1 broadly neutralizing antibody evolution - The Swiss 4.5K Screen
  • : FunderSNSF
  • : Grant ID314730_152663
  • : Project TitleThe role of humoral immunity in HIV infection - Understanding broadly neutralizing antibody evolution
  • : FunderSNSF
  • : Grant ID324730_159868
  • : Project TitleHIV-1 Transmission in Switzerland: viral transmission traits, superinfection and drug resistance
  • : FunderSNSF
  • : Grant IDBSSGI0_155851
  • : Project TitleUsing transmission networks for assessing and guiding prevention efforts in hiv
  • : FunderFP7
  • : Grant ID213744
  • : Project TitleSECURE - Security of Energy Considering its Uncertainty, Risk and Economic Implications

Download

Download PDF  'Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity'.
Preview
Content: Published Version
Filetype: PDF
Size: 4MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)