Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model
Authors and Affiliations
Authors and Affiliations
Kwang-Min Yua,b, Su-Jin Parka,b, Min-Ah Yua,b, Young-Il Kima,b, Younho Choic, Jae U. Jungc, Benjamin Brennand,1, and Young Ki Choia,b,1
a Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 28644, Republic of Korea; b Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju 28644, Republic of Korea; c Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; and d Medical Research Council–University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland, United Kingdom
1To whom correspondence may be addressed.
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.
SFTS, emerging banyangvirus, live attenuated vaccine, ferret model, bunyavirus