Development of a potent protective felinized chimeric antibody C8A8 targeting feline and canine parvovirus

Feline panleukopenia (FPL) is among the most lethal infectious diseases affecting cats, characterized by severe leukopenia, persistent fever, and life-threatening diarrhea. Currently, available clinical treatment options remain inadequate. In this study, we constructed a murine-derived, felinized chimeric antibody, C8A8. The variable region of a murine-derived neutralizing anti-feline parvovirus (FPV) monoclonal antibody was sequenced using the 5'/3' RACE method and subsequently fused with the constant region of a cat-derived monoclonal antibody. The recombinant antibody was expressed in CHO-S cells. Epitope mapping revealed that C8A8 targets a conserved epitope (residues 1-9) located at the N-terminus of the FPV VP2 protein. Affinity assays demonstrated that C8A8 exhibits high binding affinity to FPV VP2 protein, with an EC₅₀ as low as 0.038 µg/mL. In addition, C8A8 showed potent neutralizing and hemagglutination inhibition activities against FPV, raccoon dog parvovirus (RDPV), canine parvovirus type 2 (CPV-2), and its variants CPV-2a, CPV-2b, and CPV-2c. In a british shorthair cat model of FPV infection, daily administration of a low dose (2 mg/kg) of C8A8 for five consecutive days resulted in complete protection. Our results demonstrate that C8A8 exhibits broad-spectrum efficacy, low immunogenicity, and potential for large-scale production, suggesting its promise as a drug candidate for the treatment of FPV infection.