The immunogenicity and protection efficacy evaluation of mRNA vaccine candidate for severe fever with thrombocytopenia syndrome in mice.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne viral pathogen that causes Severe fever with thrombocytopenia syndrome (SFTS) in humans with a high fatality rate. Currently, there are no approved antivirals or vaccines against SFTSV. The envelope protein of SFTSV, which consists of two domains, Gn and Gc, has been investigated as a target antigen for the development of SFTSV vaccines. Here, we used an mRNA platform to develop an effective and safe SFTSV vaccine. Our mRNA vaccine candidate harbored an equal number of mRNAs individually encoding the full-length SFTSV Gn or Gc domain. These mRNAs were produced using a 5' cap, SmartCap, by in vitro transcription and then packaged with an ionizable lipid nanoparticle platform, called STLNP. Robust expression of these Gn and Gc antigens was observed when human 293 T cells were transfected with the SFTSV mRNA formulation. When mice were immunized with our SFTSV vaccine candidate, the collected serum displayed strong immunogenicity and in vitro neutralization activity against SFTSV. Thus, the immunized mice showed complete protection with a lethal dose of SFTSV, without any pathological traces of SFTSV infection-mediated tissue damage. Thus, our mRNA vaccine platform is a promising SFTS vaccine candidate for clinical development.