Authors: Chadwick Davis,
Juliette Tinker
Affiliation:
Title: Construction and Characterization of a Cholera Toxin Fusion Protein for use as a Potential Mucosal Yersinia Vaccine.
Abstract: With human population densities increasing, resistance to antibiotics escalating, and the threat of biological warfare, there is an immediate need for the production of novel vaccines to combat bacterial pathogens. The induction of specific immune responses in mucosal tissues by oral or nasal administration of vaccines is highly desirable for many reasons, especially the ability to protect from airborne or aerosolized biowarfare agents. Cholera toxin (CTx) from Vibrio cholerae is a vaccine adjuvant that has the unique ability to induce mucosal and systemic immune responses to mucosally coadministered antigens. However, these bacterial proteins are too toxic for use in humans in their native forms. To reduce toxicity and potentially heighten the specific immune response, a novel CTx chimera containing the virulence factor LcrV from disease-causing Yersinia was created. The molecule retains the native toxin binding subunit necessary for adjuvanticity but replaces the toxic moiety of CTx with LcrV, and represents a potential mucosal vaccine against the bioterror agent Y. pestis. Proper folding and composition was verified by SDS-PAGE and Western blot. In addition, chimeras were characterized for receptor binding via ELISA and mouse models show effective antibody production after intranasal immunization.