Variations in measles vaccine–specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors

BackgroundMeasles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine.ObjectiveWe sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response.MethodsWe genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus–binding domains of SLAM and CD46 to identify novel SNPs.ResultsIncreased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus–binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies.ConclusionOur data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination.Clinical implicationsUnderstanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.