Wednesday, June 20, 2007 - 9:15 AM Cottonwoods (Boise Centre on the Grove) 470
The Development of Bacterial Enterotoxin Chimeras as Potential Vaccines
Juliette K. Tinker, Boise State University, Boise, ID
Cholera toxin is a multisubunit protein toxin secreted by the pathogenic bacterium Vibrio cholerae. Binding and internalization of this toxin into intestinal epithelial cells is responsible for the destructive and often fatal secretory diarrhea resulting from ingestion of V. cholerae. Extensive characterization of this toxin has lead to the discovery that it is also a very promising immunostimulatory agent, or adjuvant, for the incorporation into vaccines. Adjuvants are “helper” substances that are included in vaccine preparations to ensure a robust immune response, and are especially important when introducing vaccines via an oral or nasal (mucosal) route. The AB5 enterotoxins, such as cholera toxin (CT) and Escherichia coli heat-labile toxin (LT), represent the most potent mucosal adjuvants identified to date, and may advance the production of novel mucosal vaccines. Oral or nasal vaccination is desirable for many reasons, including the reduced need for trained personnel, better patient compliance and decreased cost. Our laboratory has constructed chimeric protein fusions of CT, as well as LT, in an effort to produce detoxified vaccine candidates that may be administered mucosally. These molecules have a number of advantages over purified toxin or toxin components as adjuvants, including; the absence of the toxic subunit, presence of a functional receptor-binding subunit, direct attachment of the antigen of interest, and retention of intracellular trafficking motifs. We have recently constructed a cholera toxin chimera that represents a potential vaccine against the bioterror target, Yersinia pestis. In addition, research in my laboratory focuses on the development of bacterial enterotoxin chimeras as molecular tools for intracellular trafficking studies, as well as the characterization of novel bacterial toxins that may act as modulators of the immune system.