Virus envelope glycoprotein targeting bispecific T cell engager protects mice from lethal severe fever with thrombocytopenia virus infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever disease caused by the SFTS virus (SFTSV). Despite pandemic concerns arising from repeated instances of human-to-human transmission and a high fatality rate, effective anti-SFTSV interventions remain unavailable. Here, utilizing single-cell RNA sequencing (scRNA-seq) and flow cytometry data, we revealed that the deficiency and dysfunction states of T cells, particularly the impaired cytotoxicity and exhausted state of CD4+ T cells, were significantly associated with lethal consequences in SFTS patients. Using an infectious mouse model, we further observed that depletion of CD4+ T and CD8+ T cells was related to elevated viremia and increased fatality rates in SFTSV-infected mice. Accordingly, we designed virus envelope glycoprotein-targeting bispecific T cell engager (BiTE) antibodies to redirect T cells to eliminate SFTSV-infected cells, effectively rescuing mice from lethal SFTSV infection. Collectively, Gn-targeted BiTEs hold potential as a therapeutic option for treating SFTS.