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Principal Investigator: Dr. Yung Fu Chang
Contact Information: E-mail: yc42@cornell.edu - Phone: 607-253-3675
Sponsor: USDA-Federal Formula Funds
Grant Number: 2005-06-113
Title: Development of an Attenuated Vaccine against Bovine Salmonellosis
Annual Direct Cost: $25,000
Project Period: 10/01/05-09/30/08
NON-TECHNICAL SUMMARY: Salmonellosis is one of the leading causes of food borne disease in United States. Out of 1500 serovars of Salmonella, S. Typhimurium and S. Dublin are the most common serotype isolated from cattle in United States. Multiantibiotic resistance provides this organism with a survival advantage, thus hindering successful treatment of infections. Effective vaccine is necessary for the prevention of disease. The important virulence factor required for the growth of Salmonella serotype Typhimurium at systemic sites of infection in mice model are type III secretion system (TTSS) encoded by pathogenicity island 2 (SPI2) in the chromosome. These genes in Salmonella serotype Dublin also contributes to the systemic infection in calves (Bispham et al., 2001; Libby et al., 1997). The invasion-associated with TTSS-1 encoded by SPI-1 is also of equal importance for the localization at the intestinal phase by Salmonella serotype Dublin and Salmonella serotype Typhimurium. Our hypothesis is that in vivo expressed genes (ivi) are implicated in the pathogenesis of salmonellosis. Therefore, the attenuated strains of S. Typhimurium targeting TTSS will help us to develop the potential vaccine against Salmonella infection. Our preliminary results for screening the in vivo genes using signature tagged mutagenesis in S. Choleraesuis resulted in mutants targeting TTSS-2 in. To test our hypothesis, we would like to construct S. typhimurium mutants targeting TTSS and develop the attenuated strains as vaccine for salmonellosis.
OBJECTIVES: Salmonella enterica subsp enterica sv Typhimurium infection affects both humans and animals. Serovar Typhimurium has been increasingly isolated in samples taken from beef and poultry. Infection in calves usually leads to gastroenteritis but the bacteria can also survive asymptomatically resulting in a potentially serious problem for both the livestock industry and public health. Vaccinating cattle against salmonellosis could be an effective tool for the prevention of disease. Both live and killed vaccines developed so far are not effective and produce side effects. Therefore, a safe and effective attenuated vaccine is indispensable. We propose to construct double mutants in serovar Typhimurium and evaluate its efficacy and safety in a mouse model first and then in calves. Our objective is to develop attenuated vaccine strains for the prevention of Salmonella infection in cattle. The aims of our project are: 1. Generation of serovar Tyhpimurium double mutant by allelic exchange targeting aroA and yej, aroA/ssaV, ssaV and yej. The rationale to choose aroA, ssaV and yej as target genes is that these mutants have potential to serve as vaccine candidates. 2. Characterization and comparison of the immunoprotective potential of attenuated strains in a mouse model and in calves.
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