title: Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins Hospital, Baltimore, Maryland 21287-4933, USA. boger@jhmi.edu
authors.forename: Ravit
authors.initials: R
authors.lastname: Arav-Boger
authors.forename: Genevieve L
authors.initials: GL
authors.lastname: Wojcik
authors.forename: Priya
authors.initials: P
authors.lastname: Duggal
authors.forename: Roxann G
authors.initials: RG
authors.lastname: Ingersoll
authors.forename: Terri
authors.initials: T
authors.lastname: Beaty
authors.forename: Robert F
authors.initials: RF
authors.lastname: Pass
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
mesh_terms: D000328:Adult; D000483:Alleles; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000151:congenital / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology; D016023:Integrins / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000276:immunology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D016023:Integrins; D051193:Toll-Like Receptors; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051550:I-kappa B Kinase; C496565:IKBKE protein, human