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.
Dikopoulos
Nektarios
N
Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany. nektarios.dikopoulos@medizin.uni-ulm.de
Riedl
Petra
P
Schirmbeck
Reinhold
R
Reimann
Jörg
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002412:Cations / Q000276:immunology; D000939:Epitopes; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009841:Oligonucleotides / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011995:Recombination, Genetic; D013997:Time Factors; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology; D014761:Viral Hepatitis Vaccines / Q000276:immunology* / Q000494:pharmacology
D002412:Cations; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; D009841:Oligonucleotides; D015375:Receptors, Interleukin-2; D022223:Vaccines, Subunit; D014761:Viral Hepatitis Vaccines