Abstract
The phase III Thai RV144 vaccine trial showed an estimated vaccine efficacy (VE) to prevent HIV-1 infection of 31.2%, which has motivated the search for immune correlates of vaccine protection. In a recent report, several single nucleotide polymorphisms (SNPs) in FCGR2C were identified to associate with the level of VE in the RV144 trial. To investigate the functional significance of these SNPs, we utilized a large scale B cell RNA sequencing database of 462 individuals from the 1000 Genomes Project to examine associations between FCGR2C SNPs and gene expression. We found that the FCGR2C SNPs that associated with vaccine efficacy in RV144 also strongly associated with the expression of FCGR2A/C and one of them also associated with the expression of Fc receptor-like A (FCRLA), another Fc-γ receptor (FcγR) gene that was not examined in the previous report. These results suggest that the expression of FcγR genes is influenced by these SNPs either directly or in linkage with other causal variants. More importantly, these results motivate further investigations into the potential for a causal association of expression and alternative splicing of FCGR2C and other FcγR genes with the HIV-1 vaccine protection in the RV144 trial and other similar studies.
Highlights
The RV144 preventive HIV-1 vaccine efficacy trial tested the ALVAC-HIV-1 plus gp120 AIDSVAX B/E vaccine regimen in Thailand and demonstrated an estimated vaccine efficacy (VE) of 31.2% for prevention of HIV-1 infection [1]
Li et al reported that FCGR2C polymorphisms were associated with HIV-1 vaccine protection in the RV144 trial [2], but the functional significance of these polymorphisms was not established
We analyzed a large scale B cell RNA sequencing dataset of 462 individuals, and found that the FCGR2C polymorphisms associated with the expression of Fc-γ receptor (FcγR) gene FCGR2A, and very likely FCGR2C itself
Summary
The RV144 preventive HIV-1 vaccine efficacy trial tested the ALVAC-HIV-1 plus gp120 AIDSVAX B/E vaccine regimen in Thailand and demonstrated an estimated vaccine efficacy (VE) of 31.2% for prevention of HIV-1 infection [1]. Several follow-up studies were conducted to search for the correlates of risk for HIV-1 infections and to investigate the predictors and the mechanisms of the vaccine protection [2,3,4,5,6]. Li et al reported that FCGR2C (Fc fragment of IgG, low affinity IIc, receptor for (CD32)) polymorphisms associated with the HIV-1 vaccine protection [2]. FCGR2C Polymorphisms Are Linked to FcγR Expression. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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