Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine.
Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine.
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DOI：
10.1186/1756-0500-5-140
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发表时间：
2012-03-13
影响因子：
1.8
通讯作者：
Yolken, Robert H
中科院分区：
文献类型：
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作者：
Arav-Boger, Ravit;Wojcik, Genevieve L;Yolken, Robert H
背景：先天性巨细胞病毒（CMV）感染是一个重要的医学问题，目前尚无解决方案。 CMV 糖蛋白 B (gB) 疫苗在年轻女性中的临床试验显示出良好的疗效。更好地了解预防 CMV 感染的基础对于开发改进的疫苗至关重要。 结果：我们对先前接种过 3 剂 CMV gB 疫苗的 142 名女性进行了 TLR 1-4、6、7、9 和 10 中单核苷酸多态性 (SNP) 及其相关细胞内信号基因的基因分型。血小板衍生生长因子受体 (PDGFRA) 和整合素中的 SNP 也根据它们在结合 gB 中的作用进行选择。 TLR7 和 IKBKE（核因子 kappa-B 激酶亚基 epsilon 抑制剂）中的特定 SNP 与 gB 疫苗的抗体反应相关。与常见等位基因的杂合子或纯合子相比，TLR7 中四个 SNP 的次要等位基因的纯合子携带者表现出更高的疫苗接种诱导的 gB 抗体反应。 IKBKE 中的 SNP rs1953090 与第二剂至第三剂疫苗的抗体水平变化相关；随着时间的推移，次要等位基因的纯合子表现出较低的抗体反应，而主要等位基因的纯合子则表现出增加的反应。结论：这些数据有助于我们了解 CMV 疫苗免疫反应变化背后的免疫遗传学机制。
BACKGROUND: Congenital Cytomegalovirus (CMV) infection is an important medical problem that has yet no current solution. A clinical trial of CMV glycoprotein B (gB) vaccine in young women showed promising efficacy. Improved understanding of the basis for prevention of CMV infection is essential for developing improved vaccines.RESULTS: We genotyped 142 women previously vaccinated with three doses of CMV gB for single nucleotide polymorphisms (SNPs) in TLR 1-4, 6, 7, 9, and 10, and their associated intracellular signaling genes. SNPs in the platelet-derived growth factor receptor (PDGFRA) and integrins were also selected based on their role in binding gB. Specific SNPs in TLR7 and IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) were associated with antibody responses to gB vaccine. Homozygous carriers of the minor allele at four SNPs in TLR7 showed higher vaccination-induced antibody responses to gB compared to heterozygotes or homozygotes for the common allele. SNP rs1953090 in IKBKE was associated with changes in antibody level from second to third dose of vaccine; homozygotes for the minor allele exhibited lower antibody responses while homozygotes for the major allele showed increased responses over time.CONCLUSIONS: These data contribute to our understanding of the immunogenetic mechanisms underlying variations in the immune response to CMV vaccine.