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

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Nektarios DikopoulosJörg Reimann

Abstract

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...Continue Reading

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Citations

Dec 12, 2012·Transplantation·Jason M ZimmererGinny L Bumgardner
Nov 13, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Petra BochtlerJörg Reimann
Jan 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christian WahlUrsula Maria Wegenka
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Phillip H HorneGinny L Bumgardner
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nektarios DikopoulosJörg Reimann

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