HEPATITIS-B SURFACE-ANTIGEN VARIATION AND PROTECTIVE IMMUNITY

Hepatitis B surface antigen (HBsAg) particles consist predominantly of a glycoprotein of 226 amino acids which bears the B-cell epitopes imp ortant for the induction of protective antibody responses in humans. I t has been clearly shown that the region between residues 120 and 150 of the S protein represents the alpha determinants common to all hepat itis B virus (HBV) isolates and is exposed on the surface of the HBV p article. Anti-alpha antibodies protect adults against the majority of infections irrespective of the subtype of the wild-type virus. Occasio nal examples of infection positive for anti-HBs antibodies have been a ssociated with the emergence of HBV variants. In particular, asymptoma tic infections have been described in vaccinated children, an observat ion which is associated with an amino acid change in a domain critical for anti-HBs binding. Variation in amino acid sequence is also found within the preS amino terminal extensions of the S protein, although t hese do not correlate with subtypic variations among the S-antigenic d omains. There is no direct evidence that preS determinants per se may stimulate a protective immune response in humans, although the hepatoc yte attachment domain is located in the preS1 region which is conserve d between HBV isolates. The inclusion of preS specificities augments a nti-HBs responses in an experimental animal; however, at the present t ime it is unclear as to how this may best be exploited in improving he patitis B vaccines for human use. Variability in HBV envelope proteins has implications for the design of vaccination programmes and the dia gnosis of HBV infections; however, the low frequency of HBV variants e merging in the face of increasing levels of herd immunity to hepatitis B at the present time means that the extension of immunization progra mmes using existing vaccines remains a priority.