A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome

• Published in: PLoS pathogens Vol. 17; no. 2; p. e1008859
• Main Authors: Yoshikawa, Tomoki, Taniguchi, Satoshi, Kato, Hirofumi, Iwata-Yoshikawa, Naoko, Tani, Hideki, Kurosu, Takeshi, Fujii, Hikaru, Omura, Natsumi, Shibamura, Miho, Watanabe, Shumpei, Egawa, Kazutaka, Inagaki, Takuya, Sugimoto, Satoko, Phanthanawiboon, Supranee, Harada, Shizuko, Yamada, Souichi, Fukushi, Shuetsu, Morikawa, Shigeru, Nagata, Noriyo, Shimojima, Masayuki, Saijo, Masayuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2021; Public Library of Science (PLoS)
• Subjects: Animal models; Antibodies; Antibody response; Biology and Life Sciences; Complications; Conjunctivitis; Deoxyribonucleic acid; DNA; DNA vaccines; Eczema; Encephalitis; Encephalopathy; Experiments; Fetuses; Fever; Gene expression; Genomes; Glycoproteins; GPC gene; Immunogenicity; Mammalian cells; Mammals; Medicine and Health Sciences; Microscopy; Polyclonal antibodies; Proteins; Research and Analysis Methods; RNA polymerase; Side effects; Skin diseases; Smallpox; Stomatitis; Strains (organisms); Thrombocytopenia; Vaccines; Viruses; Japan
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008859

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 10 3 TCID 50 and 10 5 TCID 50 . 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.