Preclinical immunogenicity and efficacy of novel mRNA vaccine against severe fever with thrombocytopenia syndrome virus

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease caused by Bandavirus dabieense , also known as the SFTS virus (SFTSV). SFTS’ fatality rate is 10%–27%, and SFTS cases and the distribution of outbreaks are increasing, but there is no approved vaccine to prevent SFTS. Here, we examined the immunogenicity and efficacy of three lipid nanoparticle-mRNA (LNP-mRNA) vaccine candidates encoding SFTSV glycoprotein N (Gn), glycoprotein C (Gc), or nucleocapsid protein (NP) (LNP-mRNA-Gn, LNP-mRNA-Gc, and LNP-mRNA-NP, respectively) in mice. Immunization with LNP-mRNA-Gn, LNP-mRNA-Gc, or LNP-mRNA-NP alone completely protected Ifnar1 – / – mice from lethal SFTSV challenge. LNP-mRNA-Gn and LNP-mRNA-Gc also induced SFTSV-neutralizing activity in Ifnar1 – / – mice, whereas LNP-mRNA NP did not. The efficacy of LNP-mRNA-NP was abrogated by the in vivo depletion of CD4 + cells, but not CD8 + cells. These results highlight three promising candidates for effective vaccines against SFTS, each possessing a distinct protective mechanism.