Abstract
Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing 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.
Highlights
The incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available
DNA vaccines were constructed that encode full-length Gn, Gc, N, non-structural proteins (NSs), and the RNA-dependent RNA polymerase (RdRp) genes of SFTSV based on sequences of 31 clinical isolates isolated from patients in China, Korea, and Japan that were available in GenBank (Supplementary Table 1)
We examined the expression of Gn, Gc, N, NSs, or RdRp from each DNA plasmid using western blot assays (Fig. 1b)
Summary
Immunogenicity of SFTSV DNA vaccine candidates in mice. DNA vaccines were constructed that encode full-length Gn, Gc, N, NS, and the RNA-dependent RNA polymerase (RdRp) genes of SFTSV based on sequences of 31 clinical isolates isolated from patients in China, Korea, and Japan that were available in GenBank (Supplementary Table 1). When BALB/c mice (n = 3/each DNA plasmid) were immunized with individual DNA plasmid encoding Gn, Gc, N, NSs, or RdRp followed by in vivo electroporation, IFN-γ ELISPOT assays showed that strong vaccine-induced T-cell responses to desired antigen were induced (Supplementary Fig. 2a). The minimal epitope sequence (NSs247–255, YPYLMAHYL) for high-affinity binding to mouse MHC class Ι, H-2Ld was identified using in silico NetMHC 4.0 analysis and IFN-γ ELISPOT assays (Supplementary Fig. 2b–d). This was used for the synthesis of an H-2Ld dextramer (Fig. 1e).
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