Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations.
The influence of genetic variability within the major histocompatibility complex (MHC) region on variations in immune responses to childhood vaccination was investigated. The study group consisted of 135 healthy infants who had been immunized with hepatitis B (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using Illumina Goldengate MHC panels (Mapping and Exon Centric). At the 1 year post vaccination check-up total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. A number of single nucleotide polymorphisms (SNPs) within MHC Class I and II genes were found to be associated with variations in the vaccine specific antibody responses and serum levels of immunoglobulins (IgG, IgM) and IgG isotypes (IgG1, IgG4) (all at p<0.001). Linkage disequilibrium patterns and functional annotations showed that significant SNPs were strongly correlated with other functional regulatory SNPs. These SNPs were found to regulate the expression of a group of genes involved in antigen processing and presentation including HLA-A, HLA-C, HLA-G, HLA-H, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DOB, and TAP-2. The results suggest that genetic variations within particular MHC genes can influence immune response to common childhood vaccinations, which in turn may influence vaccine efficacy.
Toxicology and Molecular Biology Branch, CDC/NIOSH, Morgantown, WV, USA. Electronic address: byucesoy@cdc.gov.
Berran
B
Yucesoy
Yerkebulan
Y
Talzhanov
Victor J
VJ
Johnson
Nevin W
NW
Wilson
Raymond E
RE
Biagini
Wei
W
Wang
Bonnie
B
Frye
David N
DN
Weissman
Dori R
DR
Germolec
Michael I
MI
Luster
Michael M
MM
Barmada
D000907:Antibodies, Bacterial / Q000097:blood; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007223:Infant; D008285:Major Histocompatibility Complex; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide
D000907:Antibodies, Bacterial; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines
CPS; Childhood vaccine; DTaP; Genetic polymorphism; HBV; HBsAg; HLA; Hib; IPV; Ig; Immune response; LD; MHC; Major histocompatibility complex; OR; PCV7; PnPS; SNP; diphtheria, tetanus, and pertussis; haemophilus influenza type b; hepatitis B virus; heptavalent pneumococcal conjugate; human leukocyte antigen; immunoglobulin; inactivated polio vaccine; linkage disequilibrium; major histocompatibility complex; odds ratio; pneumococcal cell wall polysaccharide; pneumococcal polysaccharides; single nucleotide polymorphism; surface antigen of hepatitis B virus