Development of a Prophylactic mRNA Vaccine for Severe Fever with Thrombocytopenia Syndrome Using HSA based LNP

Abstract Current lipid nanoparticles (LNPs) used in mRNA vaccines typically incorporate polyethylene glycol (PEG) as a stabilizing material; however, safety concerns have prompted the search for non-PEG alternatives. Severe Fever with Thrombocytopenia Syndrome (SFTS) is a life-threatening zoonotic disease with a case fatality rate of up to 30%, and its incidence is rising in East Asia, including China, South Korea, and Japan. Despite its growing public health impact, no licensed vaccine or specific antiviral therapy is available, highlighting the urgent need for vaccine development. Human serum albumin (HSA) is a promising stabilizer, yet an HSA-based LNP mRNA vaccine has not been reported. Here, we developed SFTSV HSAmvac, an HSA-LNP mRNA vaccine encoding a modified Gn protein of SFTSV. Immunization of BALB/c and C57BL/6 mice elicited robust humoral and cellular immune responses, and vaccination of IFNAR–/– mice provided complete protection against a lethal challenge, demonstrating the potential of HSA-LNP as a safe and effective mRNA vaccine delivery platform.