The therapeutic potential of mRNA-encoded SFTSV human monoclonal antibody encapsulated lipid nanoparticle in vivo

Abstract

Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has emerged as a significant public health concern in East Asia since 2009. The high mortality rate of SFTS underscores the urgent need for effective preventive and therapeutic interventions. Although a Gn-specific human monoclonal antibody, Ab10, herein referred to as the protein S/A-TEN, has been previously reported, its development has been hindered by the economic challenges and low yields of large-scale production. To address this limitation, we developed an mRNA encapsulated lipid nanoparticle to produce SFTSV-specific human mAbs (mRNA S/A-TEN). This novel approach facilitates small-scale production, potentially enabling direct human application. The mRNA S/A-TEN antibody obtained from the injected-mouse serum showed high neutralizing antibody titers. Furthermore, we found that injecting the mRNA S/A-TEN antibody into mice that were infected with lethal SFTSV resulted in 100 % survival and assisted in a rapid recovery from organ failure. This study provides the first evidence that an mRNA-encoded SFTSV-specific human mAb can provide effective therapeutic protection against SFTSV infection, offering a promising therapeutic approach for the treatment of human SFTS.