Development of a Chimeric Vaccine Providing Protection Against the Type A ASIA/Sea-97 FMDVs in East Asia

<b>Background/Objectives:</b> Foot-and-mouth disease (FMD) remains a significant threat to livestock, particularly in the pool 1 region (East Asia), where serotype A is prevalent. Vaccination is the most effective control measure, and the selection of the appropriate vaccine strain is critical for ensuring effective protection. The A/ASIA/Sea-97 lineage (and its G1 and G2 sublineages) has been reported in this region, necessitating the development of an appropriate vaccine. This study aimed to develop a potent candidate vaccine strain capable of providing effective protection against the G1 and G2 sublineages of the A/ASIA/Sea-97 lineage. <b>Methods:</b> Chimeric vaccine development was achieved by replacing and inserting antigenic sites derived from the A/ASIA/Sea-97 G1 (VP4, VP2, and VP3) and G2 sublineage (VP1 and GH loop) strains. The candidate strains were evaluated for protective efficacy in mice and pigs. <b>Results:</b> In mice, the two candidate vaccines provided strong protection against challenge with a G1 sublineage virus (A/POC/2010) and A22 Iraq and two G2 sublineage viruses (A/YC/2017 and A/GP/2018). Subsequently, the most effective candidate was selected for testing in pigs. One month after vaccination, the pigs were protected against two A/ASIA/Sea-97 viruses (A/POC/2010 and A/GP/2018) prevalent in East Asia. <b>Conclusions:</b> These results demonstrate that the developed strain has significant potential as a vaccine against the type A FMD viruses circulating in East Asia and that vaccination with this strain could be an effective strategy for regional FMD control.