This proposal evaluated a live attenuated virus vaccine expressing porcine cytokine IL-18 in pigs that is expected to provide enhanced protection against different swine influenza virus (SIV) strains. A killed vaccine with adjuvants and a modified live attenuated virus vaccine that does not express IL-18 were used as controls. The results showed that the modified live virus expressing IL-18 was able to provide broad protection against different SIV strains including different subtype viruses, similar to the control modified live vaccine. However, the inactivated vaccine induced enhanced respiratory disease in vaccinated pigs (evidenced by enhanced lung pneumonia). While no difference was observed in efficacy between two live vaccines, this was probably due to the fact that the vaccine expressing IL-18 is too attenuated to replicate efficiently in pigs. The specific adjuvants can enhance efficacy of the whole virus inactivated vaccine when the vaccine strain does not match with the challenge virus. This study proves the concept that SIV vaccines could be improved with specific adjuvants or additional cytokines. The proposed project has improved our knowledge of influenza vaccine development to better control emerging and endemic swine influenza in US swine herds.