TY - JOUR
T1 - Replication of rubella vaccine population genetic studies
T2 - Validation of HLA genotype and humoral response associations
AU - Ovsyannikova, Inna G.
AU - Jacobson, Robert M.
AU - Vierkant, Robert A.
AU - O'Byrne, Megan M.
AU - Poland, Gregory A.
N1 - Funding Information:
We thank the Mayo Clinic Vaccine Research Group and subjects who participated in our studies. We thank V. Shane Pankratz, PhD for his assistance with this study. This work was supported by NIH grants AI 48793 , AI 33144 and 1 UL1 RR024150-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.
PY - 2009/11/16
Y1 - 2009/11/16
N2 - 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.
AB - 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.
KW - Adolescent
KW - Antibody formation
KW - HLA antigens
KW - Rubella vaccine
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U2 - 10.1016/j.vaccine.2009.08.109
DO - 10.1016/j.vaccine.2009.08.109
M3 - Article
C2 - 19761839
AN - SCOPUS:70350566164
SN - 0264-410X
VL - 27
SP - 6926
EP - 6931
JO - Vaccine
JF - Vaccine
IS - 49
ER -