Potency of a Live Attenuated GPE− Vaccine Against an Antigenically Distinct Classical Swine Fever Virus Strain in Japan

<b>Background</b>: Highly potent vaccines are essential for the effective control of classical swine fever (CSF). Since CSF re-emerged in 2018 in Japan, the live CSF virus (CSFV) vaccine-a guinea pig exaltation of Newcastle disease virus-negative strain vaccine (GPE^-, genotype 1.1)-has been applied to domestic pigs, contributing to a reduction in outbreaks. Meanwhile, the persistence and continued expansion of CSFV in wild boar populations have raised concerns regarding potential antigenic divergence. <b>Methods</b>: We systematically evaluated the neutralizing reactivity of sera from GPE^--vaccinated pigs against CSFV strains (genotype 2.1) recently circulating in Japan against identified a representative strain that showed markedly reduced neutralization. We directly assessed the protective efficacy of the GPE^- vaccine against this strain in a controlled challenge experiment. At 4 weeks post-vaccination, both vaccinated and unvaccinated pigs were orally challenged with the representative Japanese strain and monitored for 3 weeks thereafter. <b>Results</b>: Among the Japanese CSFV strains, the JPN/SM/WB/2022 isolate exhibited markedly reduced neutralizing reactivity-over 32-fold lower than that against the vaccine strain-when tested with GPE^- vaccine-induced antisera. In the experimental infection in pigs, unvaccinated pigs exhibited typical clinical signs of CSF and viremia, and two pigs reached the humane endpoint. In contrast, none of the vaccinated pigs showed any clinical signs of infection. Robust humoral and cellular immune responses were induced in vaccinated pigs, which may correlate with the observed complete protection. <b>Conclusions</b>: The GPE^- live vaccine provides protective immunity against an antigenically distinct strain, prevents disease, and limits viral spread in domestic pigs.