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Vaccination with either exogenous hepatitis B surface antigen (HBsAg) lipoprotein particles without adjuvants, or plasmid DNA encoding secreted small HBsAg stimulate long-lasting, potent antibody responses in H-2 d  (BALB/c) and C57Bl/6 (H-2 b ) mice. Vaccination with exogenous HBsAg primes MHC-I restricted cytotoxic T lymphocyte (CTL) responses to HBsAg in H-2 d  but not H-2 b  mice, while DNA vaccination primes HBsAg-specific CTL responses in both mouse strains. We defined vaccination strategies that could elicit CTL responses to exogenous HBsAg in ‘low responder’ C57Bl/6 mice. We found that the bacterial plasmid DNA itself, synthetic oligodeoxynucleotides containing immunostimulating sequences, or recombinant Th1 cytokines (IL12, IFN γ ) efficiently support priming of CTL responses to exogenous HBsAg in ‘low responder’ H-2 b  mice, but have only minor effects on CTL priming in ‘high responder’ H-2 d  mice in the high dose range tested. These molecularly well defined adjuvants can thus efficiently support priming of anti-viral T cell responses under ‘low responder’ conditions.

Enhancing the Immunogenicity of Exogenous Hepatitis B Surface Antigen-Based Vaccines for MHC-I-Restricted T Cells