Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne phlebovirus that causes lethal human disease, for which there are no licensed antiviral vaccines or therapies. Herein, we developed a live attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate expressing the SFTSV Gn/Gc glycoproteins (rVSV-SFTSV/AH12-GP). High titers of cross-protective, broadly neutralizing antibodies were elicited by a single dose of rVSV-SFTSV/AH12-GP in both immunocompetent and immunocompromised mice against multiple strains of SFTSV and the related but distinct phlebovirus Heartland virus (HRTV). Remarkably, complete protection against lethal challenge with SFTSV was conferred in young and old immunocompromised mice irrespective of any pre-existing vector-specific immunity. Collectively, these results suggest that a rVSV vector expressing SFTSV glycoproteins is a promising candidate vaccine against two emerging phleboviruses associated with severe human diseases.

To analyze the epidemiological distribution, clinical characteristics, and prognostic risk factors of patients having severe fever with thrombocytopenia syndrome (SFTS).

To establish a Cox regression model predicting risk factors for mortality in patients with severe fever with thrombocytopenia syndrome (SFTS), a total of 109 SFTS patients treated at The Second Hospital of Nanjing between June 2016 and October 2020 were included in this study. The patients were categorized into survival (n = 82) and death (n = 27) groups, and the clinical manifestations on admission and laboratory examination were collected. The factors associated with the mortality risk of SFTS patients were explored by univariate and binary logistic regression analyses. The receiver operating characteristic curve was used to evaluate the predictive value of independent influencing factors and the STFS scoring system. Univariate screening showed that the putative influencing factors were age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, invasive mechanical ventilation, continuous renal replacement therapy, application of vasoactive medications, absolute count of lymphocytes, count of platelets, and levels of albumin and D-dimer (P < 0.05). Binary logistic regression showed that age (P = 0.042), APACHE II score (P = 0.030), and vasoactive medications (P = 0.035) were independent risk factors in SFTS patients. The combined prediction equation for the mortality risk of SFTS patients was “Combined predictor = age + 3.162 × APACHE II score + 22.306 × vasoactive medications,” and the predictive value of combined predictor was greater than that of age (P = 0.004) or APACHE II score (P < 0.001). The combination of age, APACHE II score, and vasoactive medications had the highest ability to predict the risk of death. The STFS scoring system could make the clinical application of independent risk factors feasible.

Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.

Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial.