Abstract
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization's Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP102A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP102A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV.
Highlights
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus
Groups of 12 ferrets were inoculated intramuscularly (i.m.) with 2 wild-type viruses: The first, a Korean strain of Severe fever with thrombocytopenia syndrome virus (SFTSV) (CB8/2016; SI Appendix, Table S1); the second, recombinant mutant SFTS viruses from genotype D that were isolated in China
Only a few animal models, such as type I IFN-deficient [35], newborn [37], or mitomycin-treated mice [38], can recapitulate the fatal illness seen in human patients following SFTSV infection
Summary
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging viral pathogen classified within the Huaiyangshan banyangvirus species, Banyangvirus genus of the Phenuiviridae family [1]. First reported in China in 2009 [2], cases of SFTS disease and subsequent virus isolations have been described in Japan [3], South Korea [4,5,6], and more recently in Vietnam [7]. When secondary SFTS cases occurred, they were often fatal and displayed similar symptoms of infection to those seen in the index patients, presenting with high viral loads in serum and low platelet counts being reported [17]. The L segment encodes the viral RNA-dependent RNA polymerase, the M segment encodes the 2 viral envelope glycoproteins (Gn and Gc), and the S segment encodes the nucleocapsid protein (N) and a nonstructural protein (NSs) in an ambisense manner [22]
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