Enhancing the immunogenicity of exogenous hepatitis B surface antigen-based vaccines for MHC-I-restricted T cells

Vaccination with either exogenous hepatitis B surface antigen (HBsAg) lipop rotein particles without adjuvants, or plasmid DNA encoding secreted small HBsAg stimulate long-lasting, potent antibody responses in H-2(d) (BALB/c) and C57B1/6 (H-2(b)) mice. Vaccination with exogenous HBsAg primes MHC-I re stricted 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 b oth mouse strains. We defined vaccination strategies that could elicit CTL responses to exogenous HBsAg in 'low responder' C57BI/6 mice. We found that the bacterial plasmid DNA itself, synthetic oligodeoxynucleotides containi ng immunostimulating sequences, or recombinant Th1 cytokines (IL12, IFN gam ma) 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 'hig h responder' H-2(d) mice in the high dose range tested. These molecularly w ell defined adjuvants can thus efficiently support priming of anti-viral T cell responses under 'low responder' conditions.