Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.
Details
Serval ID
serval:BIB_81535AD488CF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.
Journal
The Journal of clinical investigation
Working group(s)
HVTN 505 Team
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
01/11/2019
Peer-reviewed
Oui
Volume
129
Number
11
Pages
4838-4849
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
HVTN 505 is a preventative vaccine efficacy trial testing DNA followed by recombinant adenovirus serotype 5 (rAd5) in circumcised, Ad5-seronegative men and transgendered persons who have sex with men in the United States. Identified immune correlates of lower HIV-1 risk and a virus sieve analysis revealed that, despite lacking overall efficacy, vaccine-elicited responses exerted pressure on infecting HIV-1 viruses. To interrogate the mechanism of the antibody correlate of HIV-1 risk, we examined antigen-specific antibody recruitment of Fcγ receptors (FcγRs), antibody-dependent cellular phagocytosis (ADCP), and the role of anti-envelope (anti-Env) IgG3. In a prespecified immune correlates analysis, antibody-dependent monocyte phagocytosis and antibody binding to FcγRIIa correlated with decreased HIV-1 risk. Follow-up analyses revealed that anti-Env IgG3 breadth correlated with reduced HIV-1 risk, anti-Env IgA negatively modified infection risk by Fc effector functions, and that vaccine recipients with a specific FcγRIIa single-nucleotide polymorphism locus had a stronger correlation with decreased HIV-1 risk when ADCP, Env-FcγRIIa, and IgG3 binding were high. Additionally, FcγRIIa engagement correlated with decreased viral load setpoint in vaccine recipients who acquired HIV-1. These data support a role for vaccine-elicited anti-HIV-1 Env IgG3, antibody engagement of FcRs, and phagocytosis as potential mechanisms for HIV-1 prevention.
Keywords
AIDS Vaccines/administration & dosage, AIDS Vaccines/immunology, HIV Antibodies/immunology, HIV Infections/genetics, HIV Infections/immunology, HIV Infections/prevention & control, HIV-1/immunology, Humans, Immunoglobulin G/immunology, Male, Polymorphism, Single Nucleotide, Receptors, IgG/genetics, Receptors, IgG/immunology, Risk Factors, env Gene Products, Human Immunodeficiency Virus/immunology, AIDS vaccine, AIDS/HIV, Vaccines
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2022 11:45
Last modification date
23/03/2024 7:24