Development of a DNA vaccine for SFTSV that confers complete protection against lethal infection in ferrets

Abstract

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) belonging to the Phenuiviridae family. The WHO lists SFTSV as one of the most dangerous viral pathogens, and considers it likely to cause wide epidemics in the near future. The incidence of SFTSV infection has increased from its discovery in 2012 through 2018 with a mortality rate of 10–20% and the major clinical symptoms of SFTSV infection are fever, vomiting, diarrhea, thrombocytopenia, leukopenia and multiple organ failure. However, no effective vaccines are currently available for SFTSV. Here, we describe the development of a SFTSV-specific DNA vaccine, its immunogenicity, and its protective efficacy against SFTSV lethal challenge. Vaccine candidates induced both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. To investigate the vaccine efficacy in vivo, we applied a recently developed ferret model of lethal infection that recapitulates fatal clinical symptoms in SFTSV infection in humans. Vaccinated ferrets were completely protected from lethal SFTSV challenge without developing any clinical signs. Moreover, we found that anti-envelope antibodies play an important role in protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.