Development of a Recombinant O/CATHAY Topotype Foot-and-Mouth Disease Virus as a Resource for Vaccine Matching and Efficacy Evaluation

Abstract

Foot-and-mouth disease virus serotype O remains a global threat, particularly the O/CATHAY topotype in East and Southeast Asia. Because timely access to emerging field isolates can be limited, reverse genetics provides a flexible approach for generating viruses representing selected circulating strains for vaccine matching and efficacy evaluation. Here, we generated O/CATH/APQA-V18 and evaluated its suitability for vaccine assessment in pigs. A contemporary Vietnamese O/CATHAY strain was selected based on viral protein-1 phylogenetic analysis, and its P1 capsid-coding region was incorporated into an O1 Manisa backbone using reverse genetics. The recombinant virus was characterized by real-time reverse transcription polymerase chain reaction, transmission electron microscopy, and sequence analysis. Two-dimensional virus neutralization tests using sera against O/PanAsia-2 and O/Primorsky yielded antigenic relationship values of 0.04 and 0.11, respectively, indicating poor antigenic matching. In vivo, O/CATH/APQA-V18 induced clinical signs in unvaccinated pigs, confirming its infectivity and pathogenicity. Vaccinated pigs had low neutralizing antibody titers against O/CATH/APQA-V18 before challenge, and only 25% were protected. These findings support O/CATH/APQA-V18 as a genetically defined and reproducible experimental virus for vaccine matching and protective efficacy evaluation against contemporary O/CATHAY viruses.