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An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures. Virology: An emerging tick-borne disease Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by a novel phlebovirus, is a growing global health concern. The main symptoms are high fever, low platelet and white blood cell levels, and gastrointestinal problems. The disease was first identified in China in 2009, and several SFTS epidemics have occurred in East Asia, with mortality rates of between 6 and 27 per cent. Researchers in South Korea led by Young Ki Choi at Chungbuk National University, Cheongju, review the latest research into SFTS virus and disease, including transmission, genetic diversity, epidemiology, pathology and clinical features, and pandemic potential. Animal models are helping researchers understand the virus and disease and develop treatments and vaccines.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection. Ren et al. generate a panel of monoclonal antibodies (mAbs) that recognize distinct epitopes on the glycoprotein Gn and neutralize severe fever with thrombocytopenia syndrome virus (SFTSV) by diverse mechanisms. One most potent mAb targeting the Gn domain I provides protection against lethal SFTSV infection in mice.

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), a tick-borne phlebovirus first identified in China, causes severe illness characterized by high fever, thrombocytopenia, leukopenia, and, in some cases, multi-organ failure and death. With mortality rates ranging from 5% to 30% in endemic regions, SFTSV has emerged as a significant public health threat across East Asia, including South Korea and Japan, with potential for broader outbreaks. This review synthesizes recent advances in SFTSV animal models and candidate vaccines, highlighting their contributions and limitations. Current animal models, including mice, ferrets, and non-human primates, partially replicate human disease but fail to fully recapitulate clinical manifestations, limiting their translational utility. Vaccine development has shown promise, with candidates such as mRNA, subunit, and viral vector vaccines demonstrating efficacy in preclinical studies, yet none have progressed to clinical trials. Key challenges include viral genetic diversity and immune evasion. Future research should focus on refining animal models to better mimic human pathology, developing broad-spectrum vaccines, and integrating virological and immunological insights to enhance prevention and treatment strategies for SFTSV.

Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients’ lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro . The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1 -/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.

Severe fever with thrombocytopaenia syndrome virus (SFTSV), an emerging tick-borne pathogen, causes haemorrhagic fever in infected patients and is associated with a high mortality rate in humans. The imperative need for vaccines against this lethal virus is underscored by a lack of effective preventive measures. The results of this study yield notable advancements: the successful development of an SFTSV mRNA vaccine encoding the glycoprotein C (Gc) gene, achieving N-linked glycosylation in the expressed protein. This vaccination regimen induced a balanced TH1/TH2 immune response and elicited robust levels of both cellular and humoral immunity in C57BL/6 and IFNAR−/− mice. The results of the present study demonstrate that immunization with 1 μg mRNA vaccine provides complete protection (100 %) against lethal SFTSV infection (77,000 LD50) in IFNAR−/− mice. Moreover, the vaccine candidate induces long-lasting immunity and confers protection against SFTSV for at least six months. Notably, the antibody provides 100 % protection according to passive transfer assays, suggesting that humoral immunity plays a crucial role in resisting SFTSV challenge. These findings present a promising stride forward in the quest for an effective vaccine against SFTSV, highlighting the potential of the developed mRNA vaccine in conferring substantial immunity. •Developed an SFTSV mRNA vaccine with N-glycosylation modifications to Gc gene.•Achieved 100 % protection against lethal SFTSV infection in mice with 1 μg dose.•Induced long-lasting immunity effective for at least six months post-vaccination.•Antibodies confer complete protection, underscoring humoral immunity's critical role.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne viral pathogen that causes Severe fever with thrombocytopenia syndrome (SFTS) in humans with a high fatality rate. Currently, there are no approved antivirals or vaccines against SFTSV. The envelope protein of SFTSV, which consists of two domains, Gn and Gc, has been investigated as a target antigen for the development of SFTSV vaccines. Here, we used an mRNA platform to develop an effective and safe SFTSV vaccine. Our mRNA vaccine candidate harbored an equal number of mRNAs individually encoding the full-length SFTSV Gn or Gc domain. These mRNAs were produced using a 5′ cap, SmartCap, by in vitro transcription and then packaged with an ionizable lipid nanoparticle platform, called STLNP. Robust expression of these Gn and Gc antigens was observed when human 293 T cells were transfected with the SFTSV mRNA formulation. When mice were immunized with our SFTSV vaccine candidate, the collected serum displayed strong immunogenicity and in vitro neutralization activity against SFTSV. Thus, the immunized mice showed complete protection with a lethal dose of SFTSV, without any pathological traces of SFTSV infection-mediated tissue damage. Thus, our mRNA vaccine platform is a promising SFTS vaccine candidate for clinical development.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease in China, Japan, and Korea. This study aimed to estimate the monthly SFTS occurrence and the monthly number of SFTS cases in the geographical area in Korea using epidemiological data including demographic, geographic, and meteorological factors. Important features were chosen through univariate feature selection. Two models using machine learning methods were analyzed: the classification model in machine learning (CMML) and regression model in machine learning (RMML). We developed a novel model incorporating the CMML results into RMML, defined as modified-RMML. Feature importance was computed to assess the contribution of estimating the number of SFTS cases using modified-RMML. Aspect to the accuracy of the novel model, the performance of modified-RMML was improved by reducing the MSE for the test data as 12.6–52.2%, compared to the RMML using five machine learning methods. During the period of increasing the SFTS cases from May to October, the modified-RMML could give more accurate estimation. Computing the feature importance, it is clearly observed that climate factors such as average maximum temperature, precipitation as well as mountain visitors, and the estimation of SFTS occurrence obtained from CMML had high Gini importance. The novel model incorporating CMML and RMML models improves the accuracy of the estimation of SFTS cases. Using the model, climate factors, including temperature, relative humidity, and mountain visitors play important roles in transmitting SFTS in Korea. Our findings highlighted that the guidelines for mountain visitors to prevent SFTS transmissions should be addressed. Moreover, it provides important insights for establishing control interventions that predict early identification of SFTS cases.

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS virus (SFTSV), is a tick-borne disease that poses a significant public health threat due to its high fatality rate and the lack of effective treatments or vaccines. Since its first identification, SFTSV has been reported in multiple countries, including China, South Korea, Japan, and Vietnam, highlighting its expanding regional footprint and potential global impact. This review summarizes recent preclinical and early clinical advancements in vaccine development and therapeutic strategies for SFTSV, with an emphasis on novel vaccine platforms and antiviral approaches. It also discusses the critical role of immunocompromised animal models, such as IFNAR – / – and STAT2 – / – mice, in elucidating disease mechanisms and evaluating candidate interventions. Promising vaccine platforms include mRNA-based vaccines, viral vector vaccines, protein subunit vaccines, and inactivated virus vaccines. Additionally, therapeutic approaches—such as RNA-dependent RNA polymerase (RdRp) inhibitors, calcium channel blockers, immunotherapies, targeted therapeutic strategies, and traditional Chinese medicine—have demonstrated potential in preclinical and limited clinical studies. However, challenges remain, including reduced efficacy when treatment is administered late, limited validation in human clinical trials, and the risk of viral resistance. Despite progress, key challenges persist in modeling human SFTS in animals and translating preclinical findings to clinical applications. This review underscores the urgent need for continued research to address these gaps, accelerate the development of effective countermeasures, and enhance global preparedness for future SFTSV outbreaks.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens. Methods: Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice. Results: We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response. Conclusions: Taken together, the vaccine platforms described here represent strong vaccine candidates for further development.