We have established that E. coli heat labile enterotoxin (LT) is an excellent mucosal adjuvant (immune enhancer) for stimulating immunity in young pigs and does not cause diarrhea or other adverse reactions when administered by intranasal inoculation, even at a relatively high dosage. Co-administration of LT and the K88 fimbriae from porcine enterotoxigenic E. coli (ETEC; pig scours) strains results in the production of both a intestinal and a systemic immune response and provides solid protection against subsequent challenge with an ETEC strain. Our long-term goal is to construct a multi-pathogen vaccine based on intestinal immune stimulation driven by LT as an adjuvant. The overall objective of the current proposal is to determine whether efficacious immunization against Swine Influenza (SI) can be coupled with ETEC immunization. We will produce non-infectious SI virus-like-particles and administer them along with LT and K88 in a vaccine and subsequently test for protection against the same subtype of SI virus and against ETEC. In future studies, immunization protocols will be optimized, and an assessment will be made of influenza virus strain cross protection. The currently proposed project will show whether LT adjuvant administration can serve as platform technology with which a number of vaccine products can be developed and delivered. OBJECTIVES: 1. Develop an inducible expression system to study influenza VLPs. 2. Establish efficacy of an Influenza/ETEC subunit vaccine enhanced by the use of LT as an adjuvant
