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 important for the induction of protective antibody responses in humans. It has been clearly shown that the region between residues 120 and 150 of the S protein represents the a determinants common to all hepatitis B virus (HBV) isolates and is exposed on the surface of the HBV particle. Anti-a antibodies protect adults against the majority of infections irrespective of the subtype of the wild-type virus. Occasional examples of infection positive for anti-HBs antibodies have been associated with the emergence of HBV variants. In particular, asymptomatic infections have been described in vaccinated children, an observation 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 these do not correlate with subtypic variations among the S-antigenic domains. There is no direct evidence that preS determinants per se may stimulate a protective immune response in humans, although the hepatocyte attachment domain is located in the preS1 region which is conserved between HBV isolates. The inclusion of preS specificities augments anti-HBs responses in an experimental animal; however, at the present time it is unclear as to how this may best be exploited in improving hepatitis B vaccines for human use. Variability in HBV envelope proteins has implications for the design of vaccination programmes and the diagnosis of HBV infections; however, the low frequency of HBV variants emerging in the face of increasing levels of herd immunity to hepatitis B at the present time means that the extension of immunization programmes using existing vaccines remains a priority.
Howard
C R
CR
Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, UK.
Allison
L M
LM
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D000939:Epitopes; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007110:Immunity, Active; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D014611:Vaccination
D000939:Epitopes; D006514:Hepatitis B Surface Antigens