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
Title
Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk.
Journal
The Journal of clinical investigation
Author(s)
Neidich S.D., Fong Y., Li S.S., Geraghty D.E., Williamson B.D., Young W.C., Goodman D., Seaton K.E., Shen X., Sawant S., Zhang L., deCamp A.C., Blette B.S., Shao M., Yates N.L., Feely F., Pyo C.W., Ferrari G., Frank I., Karuna S.T., Swann E.M., Mascola J.R., Graham B.S., Hammer S.M., Sobieszczyk M.E., Corey L., Janes H.E., McElrath M.J., Gottardo R., Gilbert P.B., Tomaras G.D.
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
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
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