Characterization of a neutralizing monoclonal antibody against type I feline coronavirus with post-adsorption blocking activity

Abstract

Feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by feline coronavirus (FCoV). FCoV is classified into two serotypes, with type I FCoV being predominant in natural infections. Despite its clinical significance, there is still a lack of effective preventive and therapeutic interventions for FIP. Neutralizing monoclonal antibodies (mAbs) have proven effective against various viral infections; however, no neutralizing mAbs have been developed for type I FCoV, and their potential therapeutic application for treatment of FIP remains to be explored. In this study, we generated Ya-NT-1, the first mAb capable of neutralizing type I FCoV in vitro, using a conventional hybridoma approach. Ya-NT-1 specifically recognized type I FCoV but did not react with type II FCoV, confirming its serotype specificity. However, western blot analysis failed to identify the viral structural protein targeted by Ya-NT-1, suggesting that it may recognize a conformational epitope. To investigate the mechanism of neutralization, we evaluated the ability of mAb Ya-NT-1 to block viral adsorption under different treatment conditions. Type I FCoV was effectively neutralized when the antibody was administered post-adsorption but not pre-adsorption, indicating that it acts at an early post-entry stage rather than preventing viral attachment. This suggests that Ya-NT-1 might interfere with membrane fusion or genome release, similar to previously described post-entry neutralizing antibodies against other coronaviruses. These findings represent a critical first step toward understanding the neutralization mechanisms of type I FCoV and lay the groundwork for developing antibody-based therapies for FIP. Further studies are needed to determine the precise target of Ya-NT-1 and to assess its therapeutic potential, including strategies to mitigate the risk of antibody-dependent enhancement.