Safety and efficacy of a Vero-adapted live attenuated vaccine candidate for African swine fever

African swine fever (ASF) is a lethal disease that significantly affects the global swine industry owing to the high mortality rate of infected pigs. The causative agent, ASF virus (ASFV), is difficult to control; however, live attenuated vaccines have recently emerged as a promising solution. This study evaluated the safety and efficacy of a novel live attenuated ASFV strain (VaCln3 P13) derived from a Korean ASFV isolate adapted to Vero cells. VaCln3 P13 harbors 12 non-synonymous SNPs across multiple viral genes without large gene deletions, all of which may collectively contribute to its attenuated phenotype. Notably, mutations in MGF300-2R and MGF505-7R result in protein truncation potentially influencing its safety. Our evaluation in domestic pigs inoculated with varying doses of VaCln3 P13, demonstrated substantial attenuation and protective efficacy against a virulent ASFV challenge, with only transient clinical signs and no severe adverse effects. All vaccinated pigs developed robust humoral immune responses and overcame the virulent parental virus challenge and survived, whereas mock-inoculated pigs succumbed within 10 days post-challenge. Pathological assessments revealed limited histopathological lesions in vaccinated pigs, while unvaccinated controls displayed extensive hemorrhage, lymphoid depletion, and severe systemic lesions after the challenge. These findings underscore the potential of VaCln3 P13 as a vaccine candidate for ASF control and hold promise for further applications.