Introduction: Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting cattle, pigs, and other cloven-hoofed animals. The disease, caused by FMD virus (FMDV), poses a severe threat to the livestock industry due to its ability to spread rapidly and cause high productivity losses. In India, to prevent outbreaks and safeguard animal health and productivity, a trivalent vaccine containing the inactivated virus antigens of three serotypes (O, A, and Asia-1) is employed. While humoral immunity, characterized by antibody production, is essential for defending against FMDV, a comprehensive understanding of protection also requires an investigation of cell-mediated immune (CMI) responses.

Methods: Indian cattle aged 6 to 9 months were immunized with a trivalent FMD vaccine in a water-in-oil-in-water (W/O/W) formulation. We evaluated the virus neutralizing antibody and CMI responses following vaccination. The cattle were challenged with homologous FMDV serotype O at six months post vaccination.

Results: The vaccine elicited potent humoral and cellular immune responses. The vaccine-induced virus-neutralizing antibody response peaked around two to four weeks post-vaccination and was maintained for up to six months. Elevated IFN-γ and reduced IL-4 cytokine levels by 14 days post-vaccination (dpv) and the dominance of the IgG2 isotype antibody at 30 dpv suggested a predominantly Th1-type cellular immune response. Interestingly, IFN-γ and IL-4 expression exhibited inverse patterns of regulation, highlighting the precise regulation of Th1 and Th2 responses. The challenging of vaccinated cattle with the homologous FMDV serotype O at six months post-vaccination showed 100% protective efficacy.

Conclusions: The study findings demonstrated that humoral, as well as CMI, responses with a predominant Th1 immune response contributed to the vaccine’s efficacy against the FMDV challenge in cattle.