title: Identification of potential CD8+ T-cell epitopes of the 19 kDa and AhpC proteins from Mycobacterium tuberculosis. No evidence for CD8+ T-cell priming against the identified peptides after DNA-vaccination of mice.
abstract: Mycobacterium tuberculosis is one of the major killers among infectious agents. It is of great importance to develop an efficient vaccine against M. tuberculosis since the only available vaccine, M. bovis-BCG, has a low efficacy. Furthermore, the emergence of multi-drug-resistant M. tuberculosis strains makes it difficult to cure the disease. CD8+ T cells have been implied to play an important role in protective immunity against M. tuberculosis. A good vaccination strategy for the induction of cytotoxic CD8+ T-cell responses is naked DNA-injection of eukaryotic expression vectors. The use of DNA-injection in an attempt to induce cytotoxic CD8+ T-cell responses against epitopes of the 19 kDa or AhpC proteins from M. tuberculosis in mice was studied. MHC class I binding assays, of peptides derived from these proteins, demonstrated the presence of potential CD8+ T-cell epitopes. However, CD8+ T-cell responses against the peptides after DNA-injection were not detected. Furthermore, no difference in the kinetics of bacterial clearance was observed in vaccinated versus unvaccinated animals, even though 19 kDa and AhpC specific antibodies were readily detected in the serum of vaccinated animals. Taken together these results suggest that the 19 kDa and AhpC genes are not good candidates for DNA vaccines against M. tuberculosis.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: K J
authors.initials: KJ
authors.lastname: Erb
authors.forename: J
authors.initials: J
authors.lastname: Kirman
authors.forename: L
authors.initials: L
authors.lastname: Woodfield
authors.forename: T
authors.initials: T
authors.lastname: Wilson
authors.forename: D M
authors.initials: DM
authors.lastname: Collins
authors.forename: J D
authors.initials: JD
authors.lastname: Watson
authors.forename: G
authors.initials: G
authors.lastname: LeGros
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology*; D010544:Peroxidases; D054464:Peroxiredoxins; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology*
chemical_list: C087864:19 kDa antigen, Mycobacterium; D001500:BCG Vaccine; D001426:Bacterial Proteins; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins