Comparative analysis of the efficacy of vaccines using structural protein subunits of the severe fever with thrombocytopenia syndrome virus.

The severe fever with thrombocytopenia syndrome virus (SFTSV) represents a significant emerging health threat as a tick-borne pathogen that causes SFTS, with mortality rates ranging between 10 and 30%. Despite the considerable risk presented by SFTSV, an effective vaccine has yet to be developed. Our study assessed the efficacy of recombinant protein vaccines, focusing on the purified nucleocapsid protein (NP) and surface glycoproteins (Gn and Gc), against SFTSV in both singular and combined formulations. Individual vaccinations with NP or Gn subunits yielded partial protection in type I interferon receptor-knockout (IFNAR-KO) mice, with survival rates of 66.7 and 16.7%, respectively, whereas Gc vaccination did not confer significant protection, resulting in 100% mortality similar to that of the unvaccinated control group. Notably, NP vaccination substantially enhanced antigen-specific T cell responses, and Gc vaccination exhibited strong neutralizing activity against SFTSV. Among the combined recombinant protein formulations (Gn + NP, Gc + NP, and Gn + Gc + NP) tested, the Gc + NP combination provided the highest survival rate (85.7%) following challenge with a lethal dose of SFTSV, highlighting its potential as a vaccine candidate. Longitudinal studies showed that antibody levels in both wild type C57BL/6 and IFNAR-KO mice peaked between 2 and 3 months post-vaccination and declined over time. A notable decrease in NP-specific CD8+ T cell responses was observed 6 months post-vaccination in C57BL/6 mice, while NP-specific CD4+ T cell responses persisted up to 12 months. By 12 months post-vaccination, all IFNAR-KO mice vaccinated with single subunit antigens succumbed to the virus, suggesting that effective protection against SFTS may rely on antibody responses to subunit antigens and/or CD8+ T cell activity. These findings underscore the necessity of an optimized SFTS vaccine that combines protective antigens with an adjuvant system to ensure durable humoral and cellular immunity.

Molecular and Serological Investigation of Severe Fever with Thrombocytopenia Syndrome Virus in Cats.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis in China, the Republic of Korea (ROK), and Japan. The presence of the SFTS virus (SFTSV) in companion, livestock, and wild animals has been reported. Recently, human SFTS-like clinical symptoms in cats and cheetahs have been reported in Japan. Therefore, the prevalence of the SFTSV gene or antibody in cats is important for public health as well as veterinary medicine. Materials and Methods: Sera were collected from 201 feral and house cats in the ROK in 2017. Samples were analyzed for the presence of the SFTSV gene after RT-nested PCR amplification and for anti-SFTSV antibodies after enzyme linked immunosorbent assay. Results: Eight (4.0%) and nine (4.5%) of 201 cat sera were found to be positive for the SFTSV gene and anti-SFTSV nucleocapsid protein antibodies, respectively. Specifically, 5.9% feral and 2.0% house cats were positive for the SFTSV gene, and 6.9% feral and 2.0% house cats were positive for anti-SFTSV antibodies. All sequences of the SFTSV S segment obtained were included in Japanese/Korean SFTSV clades, as opposed to the Chinese clade. Conclusions: This study constitutes the first serological study of SFTSV in house and feral cats in the ROK. Evidence of SFTSV in companion animals indicates that SFTSV can circulate in homes and that more intensive precautions and education measures are needed for companion animal guardians and veterinarians.

Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by SFTS virus (SFTSV) infection. Despite a gradual increase of SFTS cases and high mortality in endemic regions, no specific viral therapy nor vaccine is available. Here, we developed a single recombinant plasmid DNA encoding SFTSV genes, Gn and Gc together with NP-NS fusion antigen, as a vaccine candidate. The viral antigens were fused with Fms-like tyrosine kinase-3 ligand (Flt3L) and IL-12 gene was incorporated into the plasmid to enhance cell-mediated immunity. Vaccination with the DNA provides complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with a plasmid without IL-12 gene resulted in partial protection. Since we failed to detect antibodies against surface glycoproteins, Gn and Gc, in the immunized mice, antigen-specific cellular immunity, as confirmed by enhanced antigen-specific T cell responses, might play major role in protection. Finally, we evaluated the degree of protective immunity provided by protein immunization of the individual glycoprotein, Gn or Gc. Although both protein antigens induced a significant level of neutralizing activity against SFTSV, Gn vaccination resulted in relatively higher neutralizing activity and better protection than Gc vaccination. However, both antigens failed to provide complete protection. Given that DNA vaccines have failed to induce sufficient immunogenicity in human trials when compared to protein vaccines, optimal combinations of DNA and protein elements, proper selection of target antigens, and incorporation of efficient adjuvant, need to be further investigated for SFTSV vaccine development.

Severe Fever with Thrombocytopenia Syndrome Virus Infection or Mixed Infection with Scrub Typhus in South Korea in 2000-2003.

Severe fever with thrombocytopenia syndrome is a tick-borne viral disease, with a high mortality rate that was first reported in China in 2009. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a bacterium transmitted to humans through chigger mite bites. Severe fever with thrombocytopenia syndrome and scrub typhus are endemic to South Korea. To investigate evidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection or mixed infection with scrub typhus in South Korea, we examined 2,329 sera samples collected from patients presenting from November 1, 2000, to November 1, 2003, for the diagnosis of rickettisal diseases at Seoul National University, Seoul, South Korea. We found retrospective evidence of SFTSV infection or mixed infection with scrub typhus in South Korea in 2000-2003. Severe fever with thrombocytopenia syndrome virus infections in South Korea occurred before previously reported cases and were more concurrent with those in China. It is important to consider SFTSV infection in patients with scrub typhus.