The induction of neutralizing antibodies specific for foot-and-mouth disease virus (FMDV) has been the central goal of vaccination efforts against this economically important disease of cloven-hoofed animals. Although these efforts have yielded much success, challenges remain, including little cross-serotype protection and inadequate duration of immunity. Commonly, viral infections are characterized by induction of cytotoxic T lymphocytes (CTL), yet the function of CTL in FMDV immunity is poorly defined. We developed an assay for detection of CTL specific for FMDV and reported that a modified adenovirus-vectored FMDV vaccine could induce CTL activity. This allowed us to determine whether FMDV-specific CTL responses are induced during infection and to test further whether vaccine-induced CTL could protect against challenge with FMDV. We now show the induction of antigen-specific CTL responses after infection of swine with FMDV strain A24 Cruizero. In addition, we developed a vaccination strategy that induces FMDV-specific CTL in the absence of significant neutralizing antibody. Animals vaccinated using this protocol showed delayed clinical disease and significantly suppressed viremia compared to control animals, suggesting a role for CTLs in the control of virus shedding. These results provide new insights showing induction of CTL responses to FMDV following infection or vaccination, and create the potential for improving vaccine performance by targeting cellular immunity.
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