Antibody Development Strategies for SFTSV: From Hybridoma to Emerging Technologies

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne SFTS virus (SFTSV), with a case fatality rate of 16.2–32.6% in East Asia. Currently, no approved vaccines or antiviral treatments exist. Monoclonal antibody (mAb) therapy offers rapid immune protection and is a promising strategy against SFTSV. This review outlines advances in SFTSV neutralizing mAb research, covering conventional generation methods (hybridoma, phage display) and innovative approaches such as single B cell sequencing. We also introduce computational tools like artificial intelligence -assisted epitope prediction and in silico mAb design. Furthermore, we discuss the structure–function relationships of mAbs targeting Gn and Gc glycoproteins, their mechanisms (e.g., fusion inhibition, receptor blockade), and key functional attributes including breadth, potency, and cross-reactivity. Challenges such as limited epitope accessibility, immune interference, and antibody-dependent enhancement are highlighted. Finally, we propose a multipronged strategy integrating structure-guided engineering, high-throughput screening, and rigorous preclinical evaluation to accelerate the development of safe and effective SFTSV therapeutics.