An official website of the United States government.
<p>The overall objective of this project is to develop and characterize attenuated strains of Salmonella for use as live vaccine. We have developed a gidA-mnmE double knockout mutant of Salmonella Typhimurium that was highly attenuated in mice and provided protection against challenge with lethal dose of WT. This project will evaluate the potential use of gidA-mnmE mutant of Salmonella Enteritidis (SE) for immunization of chickens. Four objectives will be studied; the first objective will determine the degree of attenuation of the SE gidA-mnmE mutant using the LD50 study and host inflammatory responses using the chicken model of infection. In the second objective, the efficacy of immunization with the SE mutant will be assessed by vaccination of chickens and challenging with lethal dose of WT. Additionally, the ability of vaccination to provide protective immunity in the progeny of laying hens immunized with the SE mutant will be examined by challenging the progenies with lethal dose of WT SE. This aim will provide information on whether vaccination of breeders with the gid-mnmE mutant will protect commercial stock against SE infection. The third goal of this project is to examine if immunization with the SE mutant inhibit Salmonella colonization in chickens intestinal mucosa and internal organs such as liver, spleen and ovaries. This will be achieved by immunizing chickens with the mutant and challenging them with infectious dose of WT SE and determine bacterial load in the intestinal mucosa and the internal organs. The 4th goal will determine the immune mechanism by which immunization of chickens with the SE mutant provides protection against SE infection. This goal will be achieved by determination of the levels humoral, cell-mediated and mucosal immunity using immunoassays and flow cytometric analyses. Moreover, Th1/Th2 immune responses and activation of long-term lymphocyte memory cells will also examined. </p>
<p>NON-TECHNICAL SUMMARY: Salmonella is the most reported food-borne pathogen causing an estimated 1.4 million cases of salmonellosis with annual economic loss exceeding $1 billion. The disease is causedby consumption of contaminated beef, dairy and poultry products. Control of Salmonella in food-producing animals will significantly decrease the risk of food contamination and therefore, reduce Salmonella human outbreaks. Studies have shown that poultry products account for about 29% of all Salmonella infections and Salmonella enterica serovar Enteritidis (SE) is a major contributor to the contamination of egg shells and other poultry products leading to human outbreaks. The implementation of numerous preventative measures to reduce Salmonella contamination of shell eggs, and other poultry products, has not decreased the overall incidence of salmonellosis in US poultry. The long-term goal of this research is to develop attenuated (weakened) strains of SE that could be used as a live attenuated vaccine to protect poultry and ultimately humans against salmonellosis. Therefore, development of a quality vaccine to protect poultry against salmonellosis is the most logical strategy, leading to the reduction of Salmonella infection at the initial stage of the farm to table food processing cycle. The objectives of this study is todetermine attenuation ofthe SEmutant in chickens and subsequentlyevaluate vaccination efficacy and determine maternal protective immunity in eggs and progenies of vaccinated laying hens. Further, the ability of immunization with theSE mutant to block Salmonella colonization and sheddingin chickens. Finally, the study will determine the immune mecanisms involvedin protection provided by immunization with the SE mutant. </p>