title: Replication of rubella vaccine population genetic studies: validation of HLA genotype and humoral response associations.
abstract: Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12-18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11-19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p=0.028; 2nd cohort 20.5 IU/ml, p=0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p=0.048; 2nd cohort 25.8 IU/ml, p=0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml, p=0.021; 2nd cohort 36.2 IU/ml, p=0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p=0.011; 2nd cohort 21.4 IU/ml, p=0.032) and DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1 IU/ml, p=0.023) haplotypes with lower rubella-specific antibodies was observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Byrne
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D000483:Alleles; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics*; D059867:HLA-DP alpha-Chains; D006801:Humans; D008297:Male; D012411:Rubella Vaccine / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; C464936:HLA-B*27:05 antigen; D015796:HLA-B27 Antigen; D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; C071172:HLA-DPA1 antigen; D012411:Rubella Vaccine; C040901:rubella antibodies