title: Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge.
abstract: Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal disease for which an effective vaccine, especially against mucosal transmission, is still not available. Like many bacterial infections, antigen-specific antibody responses have been traditionally considered critical, if not solely responsible, for vaccine-induced protection against Y. pestis. Studies in recent years have suggested the importance of T cell immune responses against Y. pestis infection but information is still limited about the details of Y. pestis antigen-specific T cell immune responses. In current report, studies are conducted to identify the presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA vaccinated Balb/C mice led to reduced protection against lethal intranasal challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able to elicit CD8+ T cell immune responses against specific epitopes of this key plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA vaccine-elicited protection. Future studies in plague vaccine development will need to examine if the presence of detectable T cell immune responses, in particular CD8+ T-cell immune responses, will enhance the protection against Y. pestis in higher animal species or humans.
authors.affiliation: Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Jon D
authors.initials: JD
authors.lastname: Goguen
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma