Virus-like particles induce MHC class I-restricted T-cell responses. Lessons learned from the hepatitis B small surface antigen.

H-2d mice generated a major histocompatibility complex (MHC) class I (Ld)-restricted T-cell response of defined restriction and epitope specificity to the hepatitis B virus small surface antigen (HBsAg). Here, we compare different vaccination techniques that prime in vivo class I-restricted, murine cytotoxic T lymphocyte (CTL) precursors and specific serum antibody responses. CTL were efficiently primed by the injection of low doses of recombinant native HBsAg particles without adjuvants, by the injection of low doses of denatured HBsAg monomers without adjuvants, by infection with recombinant vaccinia virus carrying a HBsAg-encoding gene, or by intramuscular transfer of plasmid DNA encoding HBsAg under appropriate promoter control. The observation that the injection of 100 ng to 1 microgram of native HBsAg "virus-like particles' (VLP) without adjuvants is an exogenous antigen preparation that efficiently primes class I-restricted CTL responses was unexpected. It reveals a novel aspect of the immunogenicity of VLP for T cells.