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

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-DRB1*0701 and HLA-DQB1*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 DRB1*0701; DQB1*0202. The hepatitis B surface antigen vaccine antibody nonresponder group, comprising 86 individuals, were revaccinated with a novel vaccine Hep B-3, containing both preS1- and preS2-derived proteins in addition to hepatitis 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 non-responders and that 24 individuals (80%) expressed the HLA-DQB1*02 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.