1. Antibody Fc effector functions and IgG3 associate with decreased HIV-1 risk
- Author
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Neidich, Scott D., Fong, Youyi, Li, Shuying S., Geraghty, Daniel E., Williamson, Brian D., Young, William Chad, Goodman, Derrick, Seaton, Kelly E., Shen, Xiaoying, Sawant, Sheetal, Zhang, Lu, deCamp, Allan C., Blette, Bryan S., Shao, Mengshu, Yates, Nicole L., Feely, Frederick, Pyo, Chul-Woo, Ferrari, Guido, Frank, Ian, Karuna, Shelly T., Swann, Edith M., Mascola, John R., Graham, Barney S., Hammer, Scott M., Sobieszczyk, Magdalena E., Corey, Lawrence, Janes, Holly E., McElrath, M. Juliana, Gottardo, Raphael, Gilbert, Peter B., and Tomaras, Georgia D.
- Subjects
Antigens -- Health aspects ,AIDS vaccines -- Health aspects ,Single nucleotide polymorphisms -- Health aspects ,Immunoglobulin A -- Health aspects ,HIV -- Risk factors -- Health aspects ,Immunoglobulin G -- Health aspects ,Adenoviruses -- Health aspects ,Vaccines ,Clinical trials ,Genetic polymorphisms ,DNA ,Antibodies ,Transgender people ,Health care industry ,Duke University - 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 Fc[gamma] receptors (Fc[gamma]Rs), 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 Fc[gamma]RIIa 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 Fc[gamma]RIIa single-nucleotide polymorphism locus had a stronger correlation with decreased HIV-1 risk when ADCP, Env-Fc[gamma]RIIa, and IgG3 binding were high. Additionally, Fc[gamma]RIIa 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., Introduction An efficacious vaccine that provides durable immunity remains a key priority in the fight against HIV-1. One strategy to identify an efficacious vaccine regimen is the identification of immune [...]
- Published
- 2019
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