Contribution of human leukocyte antigens to the antibody response to hepatitis B vaccination

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Abstract
We present here the analysis of 86 individuals who were true antibody nonresponders to a vaccine containing hepatitis B surface antigen. The HLA type of these individuals and of 248 controls were determined by serology for HLA class I and by molecular typing for the HLA class II loci DRB1 and DQB1. Subsequent analysis of the results revealed that HLA‐DRBI*0701 and HLA‐DQB*02 were significantly associated with antibody non‐response to the “S” ‐containing vaccine compared with the HLA control population. Further, we found that the antibody non‐response was also significantly associated with the above antigens when found in linkage disequilibrium on the HLA haplotype DRB*0701; DQB1*0202. The hepatitis B surface antigen vaccine antibody nonresponder group, compriing 86 individuals, were revaccinated with a noval vaccine Hep B‐3, containing both preS1‐ and preS2‐ derived proteins in a addition to hapatitis B surface antigen, to circumvent their previous nonresponsiveness. The hepatitis B surface antigen antibody results from this group of patients show that 30 of the 86 individuals remained antibody results from this group of patients show that 30 of the 86 individuals remained antibody non‐responders and that 24 individuals (80%) expressed the HLA‐DQB1* and that 21 individuals (70%) expressed HLA‐DRB1*0701. Our results indicate that antibody nonresponse to the Hep B‐3 vaccine is significantly associated with an extended HLA haplotype B44; DRB1*0701; DQB1*0202. A possible indication of these results is that antibody nonresponse to Hep B‐3 vaccine is linked with the HLA allele DQB1*0202. These findings may have an important impact on future vaccine design.