R. Schirmbeck et al., IMMUNIZATION WITH SOLUBLE HEPATITIS-B VIRUS SURFACE PROTEIN ELICITS MURINE H-2 CLASS-I-RESTRICTED CD8-LYMPHOCYTE RESPONSES IN-VIVO( CYTOTOXIC T), The Journal of immunology, 152(3), 1994, pp. 1110-1119
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.