Intradermal Vaccination Induces Protective Immunity Against Foot-and-Mouth Disease While Mitigating Milk Yield Reduction in Ruminants

Background: Foot-and-mouth disease (FMD) is a highly contagious viral disease causing substantial economic losses in livestock. Conventional intramuscular (IM) vaccination is widely used for FMD control but may be associated with transient reductions in milk production. This study evaluated whether intradermal (ID) vaccination could induce comparable immune responses and protection while minimizing potential impacts on productivity. Methods: In cattle, the immunogenicity of an experimental bivalent ID vaccine was compared with that of a commercially available IM vaccine by measuring antibody responses for up to 140 days post-vaccination (dpv). Milk production was monitored for 7 dpv in a separate cohort of lactating cattle. Protective efficacy was evaluated in goats following ID vaccination and challenge with a 2025 Republic of Korea serotype O field isolate (O/ME-SA/Ind-2001). Results: ID vaccination induced humoral immune responses comparable to those elicited by IM vaccination throughout the 140-day observation period. Although no statistically significant difference in milk production was observed, the ID group showed a smaller numerical reduction in milk yield. Following viral challenge, ID-vaccinated goats developed rapid neutralizing antibody responses, exhibited no clinical signs, and showed lower viral RNA levels than unvaccinated controls. Conclusions: Intradermal vaccination induced long-lasting immune responses comparable to conventional IM vaccination, was associated with a smaller numerical reduction in milk yield, and protected goats against challenge with a contemporary FMDV field isolate. These findings provide preliminary evidence supporting the potential of ID vaccination as an alternative strategy for FMD control in ruminants and warrant further comparative studies with conventional IM vaccination.