Discovery and Identification of a Novel Human Monoclonal Neutralizing Antibody Targeting Domain Ⅰ of Severe Fever with Thrombocytopenia Syndrome Virus Gn.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne pathogen that causes severe fever with thrombocytopenia syndrome and posed a severe threat to public health. Our study panned and screened the phage-display antibody library constructed from the peripheral blood mononuclear cell (PBMC) from three SFTSV-infected convalescent patients. Human monoclonal antibodies (hmAbs) targeting SFTSV glycoprotein N (Gn) were isolated from the library and evaluated for binding, affinity, and neutralizing activities in vitro. Epitope identification was performed by structural model analysis, immunofluorescence and RT-qPCR. The results showed that hmAb B36 is a Gn-binding, moderately high affinity, neutralizing antibody. Moreover, hmAb B36 recognizes a conformational epitope formed by six residues on the domainⅠof the SFTSV Gn, which differs from the epitope previously reported. Among these residues, G114, L155, and S158 were identified as key sites for hmAb B36-mediated recognition. This study performed isolation and identification of a novel neutralizing antibody, offering insights for the future development of therapeutic antibody cocktails and vaccines against SFTSV.