By Joseph L Izzo, Domenic Sica, Henry R Black
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Product 7 will comprise CVD 908-htrA in which the four Hc serotypes are encoded by a single operon contained on a stabilized expression plasmid, on which transcriptional control of the operon has been optimized. These remaining 3 products will be ready for human testing by the end of the fifth year of this proposal. We expect that one or more of the second generation vaccines should result in excellent priming of the human immune system. Generate_Screen • Project Title: M. ; Professor of Medicine; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-MAY-2006 Summary: (Adapted from the Applicant's Abstract): The lung is the major portal of entry for Mycobacterium tuberculosis, the cause of human tuberculosis.
We will develop 2 "generations" of S. Typhi-based live vector vaccines. The first generation (Category 1) consists of live vectors expressing individual Hc domains from 4 serotypes; the second generation (Category 2), will yield single live vector strains expressing up to 4 different Hc serotypes. It is our intention to coadminister the final mutivalent product with a cholera-based vaccine (Project 4) against the remaining 3 serotypes. Products 1 - 4: The attenuated S. Typhi vaccine CVD 908htrA will be used as a live vector to individually express BoNT/A-Hc, BoNT/B-Hc BoNT/E-Hc.
Our preliminary data suggest that in polarized intestinal epithelial T84 cells (which contain only rare caveolae), DIGs exhibit functional and structural heterogeneity. The observed heterogeneity has elements of epithelial cell polarity, and suggests a contribution of the cytoskeleton in establishment or expression of some of the observed differences. Proposed studies will define the patterns and determinants of heterogeneity of DIGs in polarized intestinal epithelial cells with a special emphasis on DIG/cytoskeleton interactions.