A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome. 2021

Tomoki Yoshikawa, and Satoshi Taniguchi, and Hirofumi Kato, and Naoko Iwata-Yoshikawa, and Hideki Tani, and Takeshi Kurosu, and Hikaru Fujii, and Natsumi Omura, and Miho Shibamura, and Shumpei Watanabe, and Kazutaka Egawa, and Takuya Inagaki, and Satoko Sugimoto, and Supranee Phanthanawiboon, and Shizuko Harada, and Souichi Yamada, and Shuetsu Fukushi, and Shigeru Morikawa, and Noriyo Nagata, and Masayuki Shimojima, and Masayuki Saijo
Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009698 Nucleoproteins Proteins conjugated with nucleic acids. Nucleoprotein
D005260 Female Females
D000085142 Severe Fever with Thrombocytopenia Syndrome A tick-borne infection with SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME BUNYAVIRUS of the genus Phlebovirus. It is associated with fever, THROMBOCYTOPENIA; LEUKOCYTOPENIA, and multiorgan dysfunction. It is found in parts of Asia including China, Japan, Korea and Vietnam and can be transmitted from infected domestic animals and humans. SFTS Virus Infection,Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection,Infection, SFTS Virus,SFTS Virus Infections,Virus Infection, SFTS
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000956 Antigens, Viral Substances elaborated by viruses that have antigenic activity. Viral Antigen,Viral Antigens,Antigen, Viral
D014613 Vaccines, Attenuated Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity. Attenuated Vaccine,Vaccines, Live, Attenuated,Attenuated Vaccines,Vaccine, Attenuated
D014614 Vaccines, Synthetic Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified. Antigens, Synthetic,Chemical Vaccine,Chemical Vaccines,Immunogens, Synthetic,Molecular Vaccine,Molecular Vaccines,Recombinant Vaccine,Semisynthetic Vaccine,Semisynthetic Vaccines,Synthetic Antigen,Synthetic Vaccine,Synthetic Vaccines,Vaccines, Recombinant,Synthetic Antigens,Synthetic Immunogens,Vaccines, Chemical,Vaccines, Molecular,Vaccines, Semisynthetic,Antigen, Synthetic,Recombinant Vaccines,Vaccine, Chemical,Vaccine, Molecular,Vaccine, Recombinant,Vaccine, Semisynthetic,Vaccine, Synthetic
D014759 Viral Envelope Proteins Integral membrane proteins that are incorporated into the VIRAL ENVELOPE. They are glycosylated during VIRAL ASSEMBLY. Envelope Proteins, Viral,Viral Envelope Glycoproteins,Viral Envelope Protein,Virus Envelope Protein,Virus Peplomer Proteins,Bovine Leukemia Virus Glycoprotein gp51,Hepatitis Virus (MHV) Glycoprotein E2,LaCrosse Virus Envelope Glycoprotein G1,Simian Sarcoma Virus Glycoprotein 70,Viral Envelope Glycoprotein gPr90 (Murine Leukemia Virus),Viral Envelope Glycoprotein gp55 (Friend Virus),Viral Envelope Proteins E1,Viral Envelope Proteins E2,Viral Envelope Proteins gp52,Viral Envelope Proteins gp70,Virus Envelope Proteins,Envelope Glycoproteins, Viral,Envelope Protein, Viral,Envelope Protein, Virus,Envelope Proteins, Virus,Glycoproteins, Viral Envelope,Peplomer Proteins, Virus,Protein, Viral Envelope,Protein, Virus Envelope,Proteins, Viral Envelope,Proteins, Virus Envelope,Proteins, Virus Peplomer

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