Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Abstract

Significance Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging viral pathogen discovered in 2009. The virus is present in countries of East Asia and is transmitted through the bite of an infected Haemaphysalis longicornis tick. SFTSV disease is associated with high morbidity and is often fatal. Despite the incidence of disease, no antiviral therapy or vaccine has been approved for use. Here, we report and assess 2 live attenuated viruses as vaccine candidates in our recently described ferret model of infection. We show that the viruses caused no clinical disease or mortality in healthy animals. Immunized animals mounted a robust humoral immune response to a single dose of virus, and this response protected the animals from a lethal challenge. 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.