Antibody-based Therapeutic Drug Development of Feline Infectious Peritonitis (FIPV) 2866

Abstract Description Feline infectious peritonitis (FIP) is a fatal progressive viral disease, and no effective therapy and safe vaccine are available due to antibody-dependent enhancement (ADE). Feline infectious peritonitis virus (FIPV) has two serotypes but the pathogenesis of serotype I FIPVs, which are clinically predominant, is still unclear. Based on our previous study, two monoclonal antibodies (mAbs), YB4D01 and YN1E06, derived from mice immunized with serotype I FIPV spike (S) protein were able to neutralize serotype II FIPV NTU156 strain, indicating the cross-reactivity between two serotypes. The mAbs were subsequent to epitope mapping by using immunocytochemistry, western blot and cryogenic electron microscopy (cryo-EM). The variable regions of the mAbs were sequenced, and their nucleotide sequences were constructed to generate single-chain variable fragment (scFv). The neutralization assay was conducted to confirm the neutralizing ability of the scFvs. Our results showed that the epitopes of two mAbs were mapped on the domain 0 on the S proteins of both serotypes, where has not been reported, and the scFvs were proved to retain the neutralizing abilities. The efficacy and safety of the scFvs will be evaluated by ADE test. In conclusion, the corresponding epitopes may provide novel approaches for therapeutic development and more understanding of FIPV pathogenesis, and the scFvs might be potential therapeutic drugs against FIPVs. Funding Sources The present work was supported by National Science and Technology Council, Taiwan, Republic of China (ROC) (112-2313-B-002-042) and National Taiwan University (113L892503). Topic Categories Veterinary and Comparative Immunology (VET)