PLASMID DNA TO INDUCE IMMUNITY TO INTRACELLULAR PATHOGEN

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A new method of immunization for the control of infectious diseases in which naked plasmid DNA is injected as the "immunogen" has been tested in a limited number of viral models and the results of these initial studies have caused much excitement. For example, immunization with plasmid DNA encoding either the nucleoprotein or hemagglutinin proteins of the influenza virus elicits an immune response which specifically protects against subsequent flu virus challenge. Thus plasmid DNA immunization promises to offer a unique method of stimulating both cellular and humoral immune responses and it represents an attractive alternative to conventional approaches of vaccine development. Indeed, the ability to induce a specific cell mediated immune response is as yet an unfulfilled goal of many vaccine formulations acceptable for clinical use. This is a critical consideration in vaccine development. as a cell mediated immune response is required for the elimination of most intracellular pathogens. While DNA vaccination has proven to be successful for selected viral pathogens, DNA vaccination needs to be assessed for its applicability to pathogens such as intracellular bacteria and fungi for which a heightened cell mediated immunity is required for pathogen control. This application is designed to evaluate the general method of DNA vaccination using a well established model of immunity, to Listeria monocytogenes, a bacterium which is used as a prototype for the analysis of immunity to many intracellular pathogens. Immunity to this intracellular parasite is dependent on a cellular immune mechanism. Thus, we will evaluate DNA immunization especially within the context of cellular immunity, since the failure to stimulate an effective cellular immune response is a general shortcoming of nonviable vaccine formulations. PROPOSED COMMERCIAL APPLICATIONS: Immunization employing plasmid DNA promises to offer a general method for the stimulation of immunity especially a specific cell-mediated immune response. For many bacterial and fungal pathogens that can reside within an intracellular environment, no suitable vaccine exists. Although L. monocytogenes is a intracellular pathogen of limited concern to the general human population it does cause disease and death in individuals with reduced immune capacity. In addition it significantly impacts the sheep and cattle industry. Thus, a DNA vaccine for a well studied intracellular parasite has direct commercial value and may offer greater value as a demonstration of the general utility of DNA vaccine for other bacterial and fungal diseases.