A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome |
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| Authors: | Tomoki Yoshikawa Satoshi Taniguchi Hirofumi Kato Naoko Iwata-Yoshikawa Hideki Tani Takeshi Kurosu Hikaru Fujii Natsumi Omura Miho Shibamura Shumpei Watanabe Kazutaka Egawa Takuya Inagaki Satoko Sugimoto Supranee Phanthanawiboon Shizuko Harada Souichi Yamada Shuetsu Fukushi Shigeru Morikawa Noriyo Nagata Masayuki Shimojima Masayuki Saijo |
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| Institution: | 1. Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan;2. Department of Pathology, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan;3. Department of Virology, Toyama Institute of Health, Imizu-shi, Toyama, Japan;4. Department of Microbiology, Faculty of Veterinary Medicine, Okayama University of Science, Imabari-shi, Ehime, Japan;University of Texas Medical Branch / Galveston National Laboratory, UNITED STATES |
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| Abstract: | Severe fever with thrombocytopenia syndrome (SFTS) caused by a species Dabie bandavirus (formerly SFTS virus SFTSV]) is an emerging hemorrhagic infectious disease with a high case-fatality rate. One of the best strategies for preventing SFTS is to develop a vaccine, which is expected to induce both humoral and cellular immunity. We applied a highly attenuated but still immunogenic vaccinia virus strain LC16m8 (m8) as a recombinant vaccine for SFTS. Recombinant m8s expressing SFTSV nucleoprotein (m8-N), envelope glycoprotein precursor (m8-GPC), and both N and GPC (m8-N+GPC) in the infected cells were generated. Both m8-GPC- and m8-N+GPC-infected cells were confirmed to produce SFTSV-like-particles (VLP) in vitro, and the N was incorporated in the VLP produced by the infection of cells with m8-N+GPC. Specific antibodies to SFTSV were induced in mice inoculated with each of the recombinant m8s, and the mice were fully protected from lethal challenge with SFTSV at both 103 TCID50 and 105 TCID50. In mice that had been immunized with vaccinia virus strain Lister in advance of m8-based SFTSV vaccine inoculation, protective immunity against the SFTSV challenge was also conferred. The pathological analysis revealed that mice immunized with m8-GPC or m8-N+GPC did not show any histopathological changes without any viral antigen-positive cells, whereas the control mice showed focal necrosis with inflammatory infiltration with SFTSV antigen-positive cells in tissues after SFTSV challenge. The passive serum transfer experiments revealed that sera collected from mice inoculated with m8-GPC or m8-N+GPC but not with m8-N conferred protective immunity against lethal SFTSV challenge in naïve mice. On the other hand, the depletion of CD8-positive cells in vivo did not abrogate the protective immunity conferred by m8-based SFTSV vaccines. Based on these results, the recombinant m8-GPC and m8-N+GPC were considered promising vaccine candidates for SFTS. |
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