Abstract
BackgroundCongenital 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.ResultsWe 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.ConclusionsThese data contribute to our understanding of the immunogenetic mechanisms underlying variations in the immune response to CMV vaccine.
Highlights
Congenital Cytomegalovirus (CMV) infection is an important medical problem that has yet no current solution
Data from human studies suggest that single nucleotide polymorphisms (SNPs) in immune response genes may influence severity of infections and response to vaccinations such as rubella, measles and hepatitis B [9,10,11,12,13,14,15,16]
The successful glycoprotein B (gB) vaccine trial in young women provided us with a unique opportunity to determine whether antibody responses to gB vaccine were influenced by SNPs in Tolllike receptors (TLR) genes
Summary
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. The rationale for developing a CMV vaccine is based on clinical and animal studies showing that immunity to CMV reduces the frequency and severity of disease [5,6]. Data from human studies suggest that single nucleotide polymorphisms (SNPs) in immune response genes may influence severity of infections and response to vaccinations such as rubella, measles and hepatitis B [9,10,11,12,13,14,15,16]. The successful gB vaccine trial in young women provided us with a unique opportunity to determine whether antibody responses to gB vaccine were influenced by SNPs in TLR genes
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