title: Contribution of human leukocyte antigens to the antibody response to hepatitis B vaccination.
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-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.
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, London, United Kingdom.
authors.forename: A B
authors.initials: AB
authors.lastname: McDermott
authors.forename: J N
authors.initials: JN
authors.lastname: Zuckerman
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
authors.forename: S G
authors.initials: SG
authors.lastname: Marsh
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D006680:HLA Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D011498:Protein Precursors / Q000276:immunology; D014611:Vaccination
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen