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Hepatitis B third‐generation vaccines: improved response and conventional vaccine non‐response – evidence for genetic basis in humans

The lack of response to hepatitis B vaccination remains a problem for those individuals directly at risk of hepatitis B infection, particularly those who work in the health care industry. The factors associated with non‐response to hepatitis B vaccination have been investigated in 86 non‐responder health care workers who had received multiple ‘S’ vaccinations without sustained production of anti‐HBs. This group received a recently developed hepatitis B vaccine, HepageneTM, which included proteins derived from the envelope region of HBV, not present in currently licensed vaccines. The pre‐S1 and pre‐S2 proteins were included in HepageneTM in order to circumvent anti‐HBs non‐responsiveness which had previously been demonstrated in the inbred mouse model. The inclusion of these additional proteins in HepageneTM enabled some seroconverion, from non‐responder to responder; however, a proportion of the vaccinees remained non‐responders and the reasons for this have been investigated here, with reference to HLA alleles and the demographic predisposition. Here the mechanisms that underlie hepatitis B vaccine non‐response have considered the distribution of HLA alleles, age, sex, height and weight in addition to the T‐cell responses to HepageneTM derived antigens.