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

PLoS Pathog. 2021 Feb 3;17(2):e1008859. doi: 10.1371/journal.ppat.1008859. eCollection 2021 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleoproteins / immunology*
  • Phlebovirus / immunology*
  • Severe Fever with Thrombocytopenia Syndrome / immunology
  • Severe Fever with Thrombocytopenia Syndrome / prevention & control*
  • Severe Fever with Thrombocytopenia Syndrome / virology
  • Vaccines, Attenuated / administration & dosage*
  • Vaccines, Synthetic / administration & dosage*
  • Viral Envelope Proteins / immunology*

Substances

  • Antigens, Viral
  • Nucleoproteins
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • Viral Envelope Proteins

Supplementary concepts

  • SFTS phlebovirus

Grants and funding

MSa and MSh received financial supports from the Ministry of Health, Labor and Welfare of Japan (https://www.mhlw.go.jp/english/) (grant no. H26-Sinkogyousei-Shitei-002, H29-Sinkogyousei-Shitei-002, 20HA2005), and from Japan Agency for Medical Research and Development (AMED) (https://www.amed.go.jp/en/) (grant no. JP15fk0108037, JP20fk0108002, JP20fk0108081. MSa -JP17fk0108312, and JP20fk0108072). TY & NN received financial supports from the Ministry of Health, Labor and Welfare of Japan (https://www.mhlw.go.jp/english/) (grant no. H29-Sinkogyousei-Shitei-002 and 20HA2005), and from Japan Agency for Medical Research and Development (AMED) (https://www.amed.go.jp/en/) (grant no., JP17fk0108312, JP20fk0108072 and TY -JP20fk0108081). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.