P37.05
Background: Vaccine-induced IgG binding antibodies interacting with Fcγ receptors (FcγR) may reduce infection risk through antibody-dependent cellular cytotoxicity, triggering of soluble antiviral factors, or phagocytosis. The potential role of FcγR genetic variation in vaccine efficacy (VE) was previously demonstrated by the significant association of the FcγRIIc-T118I variant with VE in RV144 vaccinees. With the RV144 follow-up trial (HVTN097) commencing in Southern Africa, we considered it important to establish the FcγR genetic variability in South Africans, given that this may influence VE.
Methods: We genotyped FcγR functional variants and gene copy number in 131 South African Black individuals. The following variants were assessed: FcγRIIa-p.H131R, FcγRIIb-p.I232T, FcγRIIc-p.T118I, FcγRIIIa-p.F158V, FcγRIIIb-HNA1a/HNA1b/HNA1c, FCGR2B/C promoter variants, and genetic markers predicting FcγRIIc expression. The FcγR data from South African Black individuals were compared with that of the 1000 Genomes Project for Asians, European Caucasians and other African populations.
Results: The FcγRIIc-118I allele previously associated with VE was not detected in the 131 South African Black individuals. Furthermore, none were predicted to express the FcγRIIc protein. Genotype frequencies were significantly different when comparing South African Black individuals with Asians (FcγRIIa-p.H131R, P<0.0001; and FcγRIIIa-p.F158V, P<0.01), or with European Caucasians (FcγRIIb-p.I232T, P<0.0001; and FcγRIIIa-p.F158V, P≤0.001). Of note were the significantly different genotype frequencies between African populations (South African, Kenyan, Nigerian) for FcγRIIa-p.H131R, FcγRIIb-p.I232T, and FcγRIIIa-p.F158V, suggesting differing FcγR-mediated immune function capabilities.
Conclusions: The HVTN097 trial will commence in different African populations, who are characterized by substantial inter-population genetic diversity, which may differentially influence VE in the populations most in need of an effective HIV vaccine.
