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Abstract
Grant Number: 2R44AI053910-02 Project Title: Development and cGMP Manufacture of a Vitrified Typhoid Vaccine
PI Information: Name Title KOCHI, SIMS K. skochi@avantimmune.com Abstract: DESCRIPTION (provided by applicant): Typhoid fever is an infectious disease that annually afflicts an estimated 16 million people worldwide, resulting in 600,000 deaths. The etiologic agent of typhoid fever, Salmonella typhi (S. typhi), is transmitted to humans by the fecal-oral route through contaminated water or food. The use of antibiotics to treat typhoid fever has transformed an often fatal disease into a readily treatable condition. The recent emergence of multidrug-resistant strains of S. typhi found in regions like Southeast Asia has resulted in an increase in the incidence of severe and fatal typhoid fever as well as heightened medical concerns. These concerns may be partially addressed through the use of an effective typhoid fever vaccine that can control morbidity and mortality and limit the spread of drug resistant strains. There are limitations of commercially available vaccines to typhoid fever, which include inconvenient dosing, parenteral administration frequently associated with local reactogenicity and fever, variable protective efficacy, and unpredictable duration of immunity. AVANT Immunotherapeutics, Inc. is developing live, attenuated S. typhi Ty800 as an orally administered, single-dose vaccine against typhoid fever. Freshly prepared Ty800 was well tolerated and remarkably immunogenic when administered as a single, oral dose to eleven healthy, adult volunteers. A vigorous mucosal response was also detected within seven days of vaccination. Lyophilized Ty800 was recently manufactured for evaluation in a Phase I/I I clinical study sponsored by the Division of Microbiology and Infectious Diseases at the NIAID. Lyophilized Ty800 requires storage at -20C, requiring a "cold chain" to maintain vaccine potency. AVANT now has technology to preserve bacterial vaccines using a proprietary preservation process that markedly improves vaccine stability at room temperature. The goals of this proposal are to (1) optimize the production methodology to incorporate this innovative drying technology into the production of a thermostable formulation for Ty800; (2) develop multidose and bulk manufacturing techniques that would significantly reduce cost and manufacturing capacity needed for production of large quantities of doses; and (3) perform scale up and GMP production of preserved Ty800. Meeting these goals will facilitate the advance of Ty800 as an oral, single-dose vaccine that can be delivered outside of the storage cold chain.
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Institution: AVANT IMMUNOTHERAPEUTICS, INC. 119 4TH AVE NEEDHAM, MA 024942725 Fiscal Year: 2006 Department: Project Start: 01-JAN-2003 Project End: 31-AUG-2008 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1