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Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial.

Publication ,  Journal Article
Li, SS; Gilbert, PB; Carpp, LN; Pyo, C-W; Janes, H; Fong, Y; Shen, X; Neidich, SD; Goodman, D; deCamp, A; Cohen, KW; Ferrari, G; Hammer, SM ...
Published in: J Virol
November 1, 2019

HIV Vaccine Trials Network (HVTN) 505 was a phase 2b efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) HIV vaccine regimen. Although the trial was stopped early for lack of overall efficacy, later correlates of risk and sieve analyses generated the hypothesis that the DNA/rAd5 vaccine regimen protected some vaccinees from HIV infection yet enhanced HIV infection risk for others. Here, we assessed whether and how host Fc gamma receptor (FcγR) genetic variations influenced the DNA/rAd5 vaccine regimen's effect on HIV infection risk. We found that vaccine receipt significantly increased HIV acquisition compared with placebo receipt among participants carrying the FCGR2C-TATA haplotype (comprising minor alleles of four FCGR2C single-nucleotide polymorphism [SNP] sites) (hazard ratio [HR] = 9.79, P = 0.035) but not among participants without the haplotype (HR = 0.86, P = 0.67); the interaction of vaccine and haplotype effect was significant (P = 0.034). Similarly, vaccine receipt increased HIV acquisition compared with placebo receipt among participants carrying the FCGR3B-AGA haplotype (comprising minor alleles of the 3 FCGR3B SNPs) (HR = 2.78, P = 0.058) but not among participants without the haplotype (HR = 0.73, P = 0.44); again, the interaction of vaccine and haplotype was significant (P = 0.047). The FCGR3B-AGA haplotype also influenced whether a combined Env-specific CD8+ T-cell polyfunctionality score and IgG response correlated significantly with HIV risk; an FCGR2A SNP and two FCGR2B SNPs influenced whether anti-gp140 antibody-dependent cellular phagocytosis correlated significantly with HIV risk. These results provide further evidence that Fc gamma receptor genetic variations may modulate HIV vaccine effects and immune function after HIV vaccination.IMPORTANCE By analyzing data from the HVTN 505 efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) vaccine regimen, we found that host genetics, specifically Fc gamma receptor genetic variations, influenced whether receiving the DNA/rAd5 regimen was beneficial, neutral, or detrimental to an individual with respect to HIV-1 acquisition risk. Moreover, Fc gamma receptor genetic variations influenced immune responses to the DNA/rAd5 vaccine regimen. Thus, Fc gamma receptor genetic variations should be considered in the analysis of future HIV vaccine trials and the development of HIV vaccines.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 1, 2019

Volume

93

Issue

21

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Vaccines, DNA
  • Vaccination
  • United States
  • Receptors, IgG
  • Polymorphism, Single Nucleotide
  • Phagocytosis
  • Incidence
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, S. S., Gilbert, P. B., Carpp, L. N., Pyo, C.-W., Janes, H., Fong, Y., … Peng, X. (2019). Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial. J Virol, 93(21). https://doi.org/10.1128/JVI.02041-18
Li, Shuying S., Peter B. Gilbert, Lindsay N. Carpp, Chul-Woo Pyo, Holly Janes, Youyi Fong, Xiaoying Shen, et al. “Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial.J Virol 93, no. 21 (November 1, 2019). https://doi.org/10.1128/JVI.02041-18.
Li SS, Gilbert PB, Carpp LN, Pyo C-W, Janes H, Fong Y, et al. Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial. J Virol. 2019 Nov 1;93(21).
Li, Shuying S., et al. “Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial.J Virol, vol. 93, no. 21, Nov. 2019. Pubmed, doi:10.1128/JVI.02041-18.
Li SS, Gilbert PB, Carpp LN, Pyo C-W, Janes H, Fong Y, Shen X, Neidich SD, Goodman D, deCamp A, Cohen KW, Ferrari G, Hammer SM, Sobieszczyk ME, Mulligan MJ, Buchbinder SP, Keefer MC, DeJesus E, Novak RM, Frank I, McElrath MJ, Tomaras GD, Geraghty DE, Peng X. Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial. J Virol. 2019 Nov 1;93(21).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 1, 2019

Volume

93

Issue

21

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Vaccines, DNA
  • Vaccination
  • United States
  • Receptors, IgG
  • Polymorphism, Single Nucleotide
  • Phagocytosis
  • Incidence
  • Humans