Genetic Variants in Toll-Like Receptor 2 (TLR2), TLR4, TLR9, and FC Receptor II Are Associated with Antibody Response to Quadrivalent Meningococcal Conjugate Vaccine in HIV-Infected Youth

This study examined the association of host genetic variants with the antibody response to the quadrivalent meningococcal conjugate vaccine (MCV4) in HIV-infected youth. Genetic variants associated with severity of meningococcal disease, in-cluding the IgG Fc receptor (FCRII)-A484T, interleukin-10 (IL-10)-A1082G,-C819T, and-C627A, IL-4-C589T, mannose binding lectin-2 (MBL2)-A/O,-H/L,-P/Q, and-X/Y, toll-like receptor 2 (TLR2)-G2408A, TLR4-A12874G and-C13174T, and TLR9-T1237C and-T1486C were determined by real-time PCR (RT-PCR) for 271 HIV-infected subjects (median, 17 years). Response was defined as a>4-fold increase from entry in bactericidal antibody titers to each serogroup. General-ized estimating equation (GEE) models were used to evaluate the association of allelic variants with the immunologic re-sponse to all serogroups within each subject with and without adjusting for CD4 percentage and HIV viral load. At week 4, but not after, subjects with TLR2-2408-G/A versus-G/G genotypes and the TLR4-12874-A/A genotype were more likely to achieve a>4-fold increase overall in the four serogroups (unadjusted P of 0.006 and adjusted P of 0.008 and unadjusted P of 0.008 and adjusted P of 0.019, respectively). At week 28, the TLR9-1237 T allele was associated with enhanced antibody response (T allele versus C/C, unadjusted P of 0.014 and adjusted P of 0.009), which was maintained at week 72 (unad