ANTIBODY AND CYTOTOXIC T-CELL RESPONSES TO SOLUBLE HEPATITIS-B VIRUS (HBV) S-ANTIGEN IN MICE - IMPLICATION FOR THE PATHOGENESIS OF HBV-INDUCED HEPATITIS
R. Schirmbeck et al., ANTIBODY AND CYTOTOXIC T-CELL RESPONSES TO SOLUBLE HEPATITIS-B VIRUS (HBV) S-ANTIGEN IN MICE - IMPLICATION FOR THE PATHOGENESIS OF HBV-INDUCED HEPATITIS, Journal of virology, 68(3), 1994, pp. 1418-1425
Immune responses to components of hepatitis B virus (HBV) are assumed
to play an essential role not only in the elimination of the virus but
also in the pathogenesis of HBV-induced hepatitis. Protective humoral
immunity to HBV is mediated by immune responses to HBV surface antige
n (HBsAg). It is important to know which HBsAg preparations induce whi
ch type of cellular and humoral immune responses under which immunizat
ion conditions. We studied in BALB/c mice the humoral (antibody) respo
nse and the class I-restricted cytotoxic T-lymphocyte (CTL) response t
o different preparations of HBsAg particles: recombinant, small protei
n particles; plasma-derived, mixed particles formed by large, medium,
and small surface proteins; and different preparations of recombinant,
mixed particles formed by large and small surface proteins. Specific
antibody levels appeared in the sera of immunized mice 2 to 3 weeks af
ter immunization and were correlated with the antigen dose used for pr
iming. HBsAg-specific antibody levels were enhanced by boost injection
s or by adsorbing the antigen to aluminum hydroxide. Injected in parti
culate form without adjuvants in the dose range of 0.1 to 10 mu g per
mouse, all HBsAg preparations tested efficiently primed specific CD8() CTL of defined restriction and epitope specificity. Specific CTL rea
ctivity was detectable from 5 days to more than 4 months postimmunizat
ion. In the dose range tested, it was independent of the antigen dose
used for immunization and not enhanced by repeated boost injections. C
TL were not elicited by HBsAg adsorbed to aluminum hydroxide. We have
thus defined conditions under which HBsAg induced preferentially eithe
r a cellular immune response or a humoral immune response. These findi
ngs may be relevant for the interpretation of HBV-associated immunopat
hologic phenomena.