Abstract
Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne phlebovirus that causes lethal human disease, for which there are no licensed antiviral vaccines or therapies. Herein, we developed a live attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate expressing the SFTSV Gn/Gc glycoproteins (rVSV-SFTSV/AH12-GP). High titers of cross-protective, broadly neutralizing antibodies were elicited by a single dose of rVSV-SFTSV/AH12-GP in both immunocompetent and immunocompromised mice against multiple strains of SFTSV and the related but distinct phlebovirus Heartland virus (HRTV). Remarkably, complete protection against lethal challenge with SFTSV was conferred in young and old immunocompromised mice irrespective of any pre-existing vector-specific immunity. Collectively, these results suggest that a rVSV vector expressing SFTSV glycoproteins is a promising candidate vaccine against two emerging phleboviruses associated with severe human diseases.
Highlights
Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne arbovirus first reported in East and Central China in 2009,1 and subsequently in Korea[2] and Japan.[3]
The neutralization results were confirmed using authentic SFTSV field strain Wuhan, which is 99.3% identical to the AH12 strain in the amino acid sequence of GP,[45] showing a FRNT50 titer of 899 by recombinant vesicular stomatitis virus (rVSV)-SFTSV/ AH12-GP and 402 by rVSV-eGFP-Heartland virus (HRTV)-GP (Fig. 3c). These results suggest that the SFTSV and HRTV glycoproteins expressed by rVSV
The group of mice that received sera from rVSV-SFTSV/AH12-GP-immunized mice exhibited slower weight loss and 60% survived the challenge, while the other 40% died during day 7–8 (Fig. 4h,i). These results further suggest that rVSV-SFTSV/AH12-GP could elicit strong humoral immunity in mice, which plays a key role in protection against npj Vaccines (2019) 5
Summary
Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne arbovirus first reported in East and Central China in 2009,1 and subsequently in Korea[2] and Japan.[3]. All the rVSV-SFTSV/AH12-GP immunized mice survived without any obvious clinical signs or significant weight loss, while the control (untreated) group died on day 3–4 post challenge (Fig. 4f,g) These results suggest that rVSV-SFTSV/AH12-GP can be delivered by many routes without affecting its protective efficacy. Reports from hospitals suggest that most of the SFTSV patients are elderly with a median age of 61 years old.[1] To test the efficacy of vaccine in the target elderly population, 8–9-month-old IFNAR−/− mice were immunized with 2 × 104 PFU of rVSV-SFTSV/AH12-GP or rVSV-eGFP-HTNV-GP, i.p. No obvious weight loss was detected in the animals during the monitoring period of 1 week (Fig. 6a). These results suggest that rVSV-SFTSV/AH12-GP is effective in aged mice and is a promising candidate for further development given that the elderly patients are at high risk of mortality upon SFTSV infection
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