A replicating RNA vaccine protects against severe fever with thrombocytopenia syndrome virus infection in mice.

No approved vaccines are currently available for Severe fever with thrombocytopenia syndrome virus (SFTSV). SFTSV is a tick-borne RNA virus with a case fatality rate ranging from 5 to 30% and is considered by the WHO to be a priority pathogen. Here, we evaluated a replicating RNA (repRNA) vaccine for protection against lethal SFTSV challenge in mice. We found that a repRNA-expressed SFTSV nucleoprotein (repNP) or glycoprotein precursor (repGPC) could confer protection, identifying both as protective antigens for SFTSV vaccine development. Furthermore, protection by our repNP vaccine required the intracellular Fc receptor TRIM21 for optimal protection, expanding the role of anti-NP antibodies and TRIM21 in control of bunyaviruses. Our data support continued development of this vaccine for SFTSV.