Back to Search
Start Over
FCGR2C polymorphisms associate with hiv-1 vaccine protection in rv144 trial
- Source :
- Journal of Clinical Investigation. September 1, 2014, Vol. 124 Issue 9, p3879, 12 p.
- Publication Year :
- 2014
-
Abstract
- The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor-mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one FCGR2C tag SNP (rs114945036) that associated with VE against HIV-1 subtype CRF01_AE, with lysine at position 169 (169K) in the V2 loop (CRF01_AE 169K). Individuals carrying CC in this SNP had an estimated VE of 15%, while individuals carrying CT or TT exhibited a VE of 91%. Furthermore, the rs114945036 SNP was highly associated with 3 other FCGR2CSNPs (rs138747765, rs78603008, and rs373013207). Env-specific IgG and IgG3 Abs, IgG avidity, and neutralizing Abs inversely correlated with CRF01_AE 169K HIV-1 infection risk in the CT- or TT carrying vaccine recipients only. These data suggest a potent role of Fc-γ receptors and Fc-mediated Ab function in conferring protection from transmission risk in the RV144 VE trial.<br />Introduction The Thai phase III RV144 vaccine trial, which tested the ALVACHIV (vCP1521) prime and bivalent clade B/E recombinant gp120 boost vaccine regimen, showed an estimated vaccine efficacy (VE) of [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 124
- Issue :
- 9
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.382429635
- Full Text :
- https://doi.org/10.1172/JCI75539