IMMUNIZATION WITH SOLUBLE HEPATITIS-B VIRUS SURFACE PROTEIN ELICITS MURINE H-2 CLASS-I-RESTRICTED CD8-LYMPHOCYTE RESPONSES IN-VIVO( CYTOTOXIC T)

Immunization with soluble proteins only rarely induces a.specific resp onse of CD8+ CTL. We describe experiments that demonstrate the efficie nt and specific in vivo priming of CTL in BALB/c mice immunized with s oluble hepatitis B virus (HBV)-derived surface (S) protein. A single ( s.c., i.p. or i.v.) injection of a low dose (30 ng to 3 mug per mouse) of recombinant S protein particles without adjuvants induced a CTL re sponse. This specific cytotoxic response was read out against a panel of different S protein-expressing transfected mouse cell lines. Effect or cells of this response were L(d)-restricted, CD3+ CD4- CD8+ CTL. H- 2d/L(d+) (BALB/c, C.B-17) mice were responders; H-2d/L(d-) (dm2) mutan t mice and H-2b (C57BL/6) mice were nonresponders. Injections of vario us dosages of a S protein-derived, immunogenic, synthetic peptide into BALB/c mice by various routes did not prime CTL. After incorporation of S protein particles into IFA or aluminum hydroxide, these protein A g lost their ability to specifically stimulate CTL in vivo. After prim ing of mice with S protein emulsified in IFA or adsorbed to aluminum h ydroxide boost injections with native S protein particles were ineffic ient in stimulating a specific CTL response. These findings are of rel evance for the design of synthetic subunit vaccines for which specific stimulation of CD8+ T effector functions is desired.