Human leukocyte antigens influence the immune response to a pre-S/S hepatitis B vaccine

In this study we investigated the effects of a single pre-S/S (Hepagene) revaccination in a large population of multiple 'S' vaccinated anti-HBs antibody nonresponder individuals (< 3 IU/l). We investigate the influence of vaccine dose (5, 10, 20 and 40 micrograms/ml), number of previous 'S' containing vaccinations and the individuals HLA genotype on both B- and T-cell responses. We show that 76% of persistently nonresponder individuals produce anti-HBs antibody (> 3 IU/l) following a single revaccination with Hepagene. This anti-HBs antibody response was dose dependent. The group that received 5 micrograms/ml of Hepagene vaccine produced significantly less anti-HBs antibody than those receiving 10, 20 and 40 micrograms/ml doses (p < 0.05 in all cases). Individuals homozygous for HLA-DRB1*0701; DQB1*0202 failed to produce > 100 IU/l of anti-HBs antibody, whereas, heterozygous individuals required > 10 micrograms/ml Hepagene vaccine. The T-cell responses to Hepagene were exclusive of the dose and magnitude of anti-HBs antibody responses. There was a trend towards increased stimulation indices in those individuals who received repeated 'S' containing vaccines. We have clearly shown that the immune response to Hepagene is influenced by the HLA genotype of the individual. However, further investigation is required to determine the specific role of these molecules in hepatitis B vaccine nonresponse. Hepagene is a registered trademark of Hedeva Pharma Ltd.