ANTIBODY AND CYTOTOXIC T-CELL RESPONSES TO SOLUBLE HEPATITIS-B VIRUS (HBV) S-ANTIGEN IN MICE - IMPLICATION FOR THE PATHOGENESIS OF HBV-INDUCED HEPATITIS

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.