Project Summary/Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging tick-borne infectious disease caused by SFTS virus (SFTSV). SFTSV is listed in the most dangerous viral pathogens by the WHO that most likely cause wide epidemics in the near future. The incidence of SFTSV infection has continuously increased up to more than 5,000 humans with a mortality rate ranging from 12% to as high as 30%. SFTSV induces a characteristic thrombocytopenia that is remarkably similar to viral hemorrhagic fevers. Infected ticks are the major source of human SFTSV infection. Particularly, the recent spread of this tick to over 12 states of USA increases the potential for outbreaks of the disease beyond the Far East Asia. The sero-prevalence of SFTSV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. No effective vaccines are currently available for SFTSV. The goal of this proposal is to comprehensively test and compare the immunogenicity and protection efficacy of four SFTSV- specific vaccine candidates against lethal SFTSV infection in age-dependent ferret model.