The efficacy of the hepatitis B vaccine can be
attributed to its ability to induce protective neutral-
izing antibodies to an antigenic region of the HBsAg
protein referred to as the ‘a’ determinant [6–8]. An
important concern for HBV immunization
programmes is what effect the emergence of hepatitis
B variants harbouring altered HBsAg proteins with
reduced antigenicity and the ability to escape neutral-
ization may have on the long-term success of these
programmes. It is clear that these variants are selected
following immunization of infected individuals. The
‘a’ determinant is a highly conformational region of the
HBsAg protein and mutations in and around the ‘a’
determinant have been shown to alter the antigenicity
of the HBsAg protein and, consequently, antibodies
against HBsAg (anti-HBs) fail to neutralize HBV
[9–13] resulting in infection of vaccinated individuals
[11,14]. In fact, a mutation of even a single amino acid
residue within this region is sufficient to result in
failure of anti-HBs to neutralize the virus. Some of the
commonly reported HBsAg mutations with the poten-
tial to escape neutralization by vaccine-induced
antibody include sG145R, sD144A, sP142S, sK141E,
sQ129H, sI/T126N/A and sM133L [10,12]. The
sG145R variant has been associated with high levels of
viraemia and persistence for up to 8 years, suggesting
that once such viruses emerge in a population they are
likely to persist for extended periods.