Eighteen swine were divided into 5 groups of 3 or 4 animals each. The animals in each group were cohoused in a separate room. All groups were inoculated via intramuscular injection in the neck area. Group 1 was a mock control group inoculated with 2 mL of saline. As negative controls, groups 2 and 3 were inoculated with 5 · 10 9 CFU of S. choleraesuis C500 or LacZ/S. cho in 2 mL of saline, respectively. Group 4 was inoculated with 5 · 10 9 CFU of p3D-NT56/S. cho in 2 mL of saline. Group 5 was treated with a high dose of p3D-NT56/S. cho containing 5 · 10 10 CFU in 2 mL of saline. After 24 h, all animals were challenged via intramuscular injection with 100 ID 50 of HKN/2002 in 2 mL of PBS in the neck area. To avoid overexposure to the challenge virus, animals that developed disease were moved to another room, and then observation proceeded. After challenge, the animals were examined daily for clinical signs of FMD, including an increase in body temperature (above 40°C) and the appearance of vesicles on the mouth and feet. The lesion score was determined at various time points post-challenge by determining the number of digits plus mouth with vesicles for each animal. The observations were terminated on day 14 post-challenge, when the animals were humanely killed.