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.

严重发烧伴血小板减少病毒 (SFTSV) 是一种新出现的蜱传白斑病毒，可导致致命的人类疾病，目前尚无获得许可的抗病毒疫苗或疗法。在此，我们开发了一种基于活减毒重组水泡性口炎病毒（rVSV）的候选疫苗，表达SFTSV Gn/Gc糖蛋白（rVSV-SFTSV/AH12-GP）。单剂量的 rVSV-SFTSV/AH12-GP 在免疫功能正常和免疫功能低下的小鼠中诱导出针对多种 SFTSV 毒株和相关但不同的静脉病毒 Heartland 病毒 (HRTV) 的高滴度交叉保护性、广泛中和性抗体。值得注意的是，无论是否存在任何预先存在的载体特异性免疫，年轻和年老的免疫受损小鼠都能获得针对SFTSV致命攻击的完全保护。总的来说，这些结果表明表达SFTSV糖蛋白的rVSV载体是针对两种与严重人类疾病相关的新出现的静脉病毒的有前途的候选疫苗。