Identification of Coxiella burnetii CD8+ T-Cell Epitopes and Delivery by Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model

摘要

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.