A model will be developed to create effective vaccine vectors which will elicit mucosal (secretory) immunity. Recombinant vaccinia virus which express one or more antigens of the pseudorabies virus (PRV) will be used as the prototype in the design of the first generation vectors. The LD (the dose lethal for 50% of animals challenged) of PRV in mice will first be determined after intraperitoneal, oral and nasal administration of PRV. The dose determined for each route will then be used to challenge mice which have been previously vaccinated intraperitoneally, orally or nasally, with vaccinia/PRV recombinants. The ratio of the number of animals which survive challenge to those which succumb will indicate the feasibility of using this vaccinia/PRV system in the design of a model to test the efficacy of these viral vectors for use as mucosal vaccines. The development of vaccines which are capable of stimulating secretory immunity will be important in protecting against infection by a variety of pathogens whose initial route of entry into the host is via mucosal surfaces.
