VACCINE VECTORS TO STIMULATE MUCOSAL IMMUNITY

A MODEL WILL BE DEVELOPED TO CREATE EFFECTIVE VACCINE VECTORS THAT WILL ELICIT MUCOSAL (SECRETORY) IMMUNITY. RECOMBINANT VACCINIA VIRUS THAT EXPRESS ONE OR MORE ANTIGENSOF THE PSEUDORABIES VIRUS (PRV) WILL BE USED AS THE PROTOTYPE IN THE DESIGN OF THE FIRST-GENERATION VECTORS. THE LD50 (THE DOSE LETHAL FOR 50 PERCENT OF THE 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 THAT HAVE BEEN PREVIOUSLY VACCINATED INTRAPERITONEALLY, ORALLY, OR NASALLY WITH VACCINIA/PRV RECOMBINANTS. THE RATIO OF THE NUMBER OF ANIMALS THAT SURVIVE CHALLENGE TO THOSE THAT 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 THAT 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.