The experiments outlined in this application will be conducted in order to assess the potential of using bacterial flagella as carriers of foreign antigenic determinants. Recombinant DNA techniques will be used to construct and express hybrid flagellin molecules encoding foreign epitopes which can assemble into flagella on the external surface of bacterial cells. Experiments will also be performed to determine the maximum amount of foreign DNa which can be inserted into the flagellin gene, as well as the minimal flagellin sequences required for assembly into external flagellar filaments. These recombinant flagella will then be isolated and purified as particulate preparations and administered to experimental animals in order to assess immunogenicity. In addition, live, attenuated Salmonella expressing these recombinant constructions will be administered to animals, and the types and magnitudes of the responses which are induced will be measured. Subunit vaccines designed to stimulate an immune response to a single antigen are attractive because of their purity in respect to both control of manufacturing and their lack of unwanted biological sequallae which can limit vaccine effectiveness and safety. The ability to easily purify recombinant flagella and administer them as particulate immunogens, and the ability to utilize live bacteria to deliver these immunogens and induce a variety of immune responses, would make this technology an attractive means to develop and manufacture new and effective vaccines.
