title: Identification of Coxiella burnetii CD8+ T-Cell Epitopes and Delivery by Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model.
abstract: Coxiella burnetii is a gram-negative bacterium that causes acute and chronic Q fever. Because of the severe adverse effect of whole-cell vaccination, identification of immunodominant antigens of C. burnetii has become a major focus of Q fever vaccine development. We hypothesized that secreted C. burnetii type IV secretion system (T4SS) effectors may represent a major class of CD8+ T-cell antigens, owing to their cytosolic localization. Twenty-nine peptides were identified that elicited robust CD8+ T-cell interferon γ (IFN-γ) recall responses from mice infected with C. burnetii. Interestingly, 22 of 29 epitopes were derived from 17 T4SS-related proteins, none of which were identified as immunodominant antigens by using previous antibody-guided approaches. These epitopes were expressed in an attenuated Listeria monocytogenes vaccine strain. Immunization with recombinant L. monocytogenes vaccines induced a robust CD8+ T-cell response and conferred measurable protection against C. burnetii infection in mice. These data suggested that T4SS effectors represent an important class of C. burnetii antigens that can induce CD8+ T-cell responses. We also showed that attenuated L. monocytogenes vaccine vectors are an efficient antigen-delivery platform that can be used to induce robust protective CD8+ T-cell immune responses against C. burnetii infection.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Gregory
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.|Department of Clinical Laboratory, 105th Hospital of the People's Liberation Army, Hefei, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Bohai
authors.initials: B
authors.lastname: Wen
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Portnoy
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan.
authors.forename: James E
authors.initials: JE
authors.lastname: Samuel
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016997:Coxiella burnetii / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D059425:Interferon-gamma Release Tests; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011778:Q Fever / Q000276:immunology / Q000382:microbiology; D000069319:Type IV Secretion Systems / Q000737:chemistry / Q000276:immunology; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D000069319:Type IV Secretion Systems; D014613:Vaccines, Attenuated
keywords: CD8+ T-cell epitopes; Q fever; antigen presentation; protective immunity; type IV secretion system effector