Ovsyannikova Inna G, Salk Hannah M, Larrabee Beth R, Pankratz V Shane, Poland Gregory A
Mayo Clinic Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 1st Street S.W., Rochester, Minnesota, 55905, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
Immunogenetics. 2015 Oct;67(10):547-61. doi: 10.1007/s00251-015-0864-z. Epub 2015 Sep 2.
The observed heterogeneity in rubella-specific immune response phenotypes post-MMR vaccination is thought to be explained, in part, by inter-individual genetic variation. In this study, single nucleotide polymorphisms (SNPs) and multiple haplotypes in several candidate genes were analyzed for associations with more than one rubella-specific immune response outcome, including secreted IFN-γ, secreted IL-6, and neutralizing antibody titers. Overall, we identified 23 SNPs in 10 different genes that were significantly associated with at least two rubella-specific immune responses. Of these SNPs, we detected eight in the PVRL3 gene, five in the PVRL1 gene, one in the TRIM22 gene, two in the IL10RB gene, two in the TLR4 gene, and five in other genes (PVR, ADAR, ZFP57, MX1, and BTN2A1/BTN3A3). The PVRL3 gene haplotype GACGGGGGCAGCAAAAAGAAGAGGAAAGAACAA was significantly associated with both higher IFN-γ secretion (t-statistic 4.43, p < 0.0001) and higher neutralizing antibody titers (t-statistic 3.14, p = 0.002). Our results suggest that there is evidence of multigenic associations among identified gene SNPs and that polymorphisms in these candidate genes contribute to the overall observed differences between individuals in response to live rubella virus vaccine. These results will aid our understanding of mechanisms behind rubella-specific immune response to MMR vaccine and influence the development of vaccines in the future.
MMR疫苗接种后风疹特异性免疫反应表型中观察到的异质性，部分原因被认为是个体间的基因变异。在本研究中，分析了几个候选基因中的单核苷酸多态性（SNP）和多个单倍型与多种风疹特异性免疫反应结果的关联，包括分泌的IFN-γ、分泌的IL-6和中和抗体滴度。总体而言，我们在10个不同基因中鉴定出23个SNP，它们与至少两种风疹特异性免疫反应显著相关。在这些SNP中，我们在PVRL3基因中检测到8个，在PVRL1基因中检测到5个，在TRIM22基因中检测到1个，在IL10RB基因中检测到2个，在TLR4基因中检测到2个，在其他基因（PVR、ADAR、ZFP57、MX1和BTN2A1/BTN3A3）中检测到5个。PVRL3基因单倍型GACGGGGGCAGCAAAAAGAAGAGGAAAGAACAA与较高的IFN-γ分泌（t统计量4.43，p < 0.0001）和较高的中和抗体滴度（t统计量3.14，p = 0.002）均显著相关。我们的结果表明，在已鉴定的基因SNP之间存在多基因关联的证据，并且这些候选基因中的多态性导致了个体间对风疹活病毒疫苗反应的总体差异。这些结果将有助于我们理解风疹特异性免疫反应对MMR疫苗的机制，并影响未来疫苗的开发。
