Novel peptide-based vaccines efficiently prime murine "help"-independent CD8+ T cell responses in the liver

Vaccines for the prophylactic and/or therapeutic immunization against hepatotropic pathogens (e.g., hepatitis B and hepatitis C virus) should establish long-lasting, specific antiviral effector/memory CD8(+) T cell immunity in the liver. We describe a novel peptide-based vaccine in which antigenic major histocompatibility complex Class I-binding peptides are fused to a cationic (e.g., human immunodeficiency virus tat-derived) domain and complexed to immune-stimulating oligonucleotides. This vaccine formulation efficiently primes liver-homing, Class I-restricted CD8(+) effector/memory T cell responses. In different antigen systems, this formulation was more potent in priming liver-homing CD8(+) T cell responses than DNA-based vaccines delivering the same epitopes. CD8(+) T cell priming was independent of CD4(+) T cell "help" but submitted to regulatory control by CD25(+) CD4(+) T cells. The vaccine efficiently primed memory/effector CD8(+) T cells detectable in the liver for more than 3 months after a single injection. With increasing time after priming, the phenotype of these specific memory CD8(+) T cells shifted from an effector memory to a central memory type. The vaccine could override T cell tolerance in mice expressing the relevant antigen from a transgene in the liver. The CD8(+) T cell immunity in the liver primed by this peptide formulation could be boosted by challenge injections. In conclusion, we describe a simple and potent vaccine formulation that has the potential to generate or reconstitute specific CD8(+) T cell immunity to hepatotropic pathogens in the liver.