CoPIs: Anatole Krattiger (Arizona State University); Roy Curtiss III (Arizona State University)
Chickens are a primary and the fastest growing source of protein in much of the developing world. Unfortunately, one organism, Salmonella gallinarum, which is widely prevalent in developing countries, causes fowl typhoid disease with devastating consequences in poultry. Vaccination against fowl typhoid is an effective approach in preventing this disease. This basic research project utilizes innovative mutational strategies and techniques for developing a live attenuated Salmonella gallinarum vaccine. Such a vaccine could have the added benefit of protecting against Salmonella pullorum, another poultry pathogen and against the human diarrheal pathogen Salmonella enteriditis, which colonizes chickens and can be transmitted to humans via contaminated eggs and meat.
Broader Impacts: A long-term result of this basic science project will be the availability of a vaccine that will distributed locally to villages where it can be easily applied to small, backyard flocks. It is the hope that this will lead to a more plentiful and reliable food supply, thus combating malnutrition, particularly in the poorer rural and urban areas of the developing world. Because increased egg and poultry productivity also results in surplus that can be sold, the project could directly contribute to poverty alleviation. The results will also lead to a safer food supply by reducing the transmission of diarrheal bacterial pathogens via food. This project involves international collaborators in developing countries and local outreach activities in the US. Scientific demonstrations will be given in the Arizona community (including local high schools), and at the local science center where a large cross section of the population is exposed to the research at the Biodesign Institute on the ASU campus. This project will also support an active program of undergraduate research and all data will deposited in and shared via public databases.
Poultry meat and eggs are a primary food source in the developing world. Fowl typhoid is a septicemic disease of poultry cause by Salmonella Gallinarum, resulting significant morbidity and mortality, which can reach as high as 100%. While this disease has been nearly eradicated in the developed world, it represents a growing economic problem in parts of the developing world where poultry plays an important contribution to the household community and more so in relative terms in poorer areas. Poultry systems are low-input, low-output systems but provide eggs and live birds for consumption, sale, barter, or ceremonies. Salmonella is prevalent in the environment, making it difficult to control, particularly in backyard flocks (Figure 1) The goal of our work was to investigate genetic mutations in S. Gallinarum that would eliminate its virulence, a property called attenuation, while allowing the strain to induce a strong anti-Salmonella immune response. Such mutants would then be viable candidates for development as vaccines to prevent fowl typhoid. In the course of our studies, we constructed a number of S. Gallinarum mutant strains carrying deletions in specific genes and/or carrying regulated delayed attenuation mutations. Some of the mutations did not impact virulence, making them unsuitable for use as vaccines. Some were attenuated, but did not confer protection. However, we identified five mutant strains that did not cause disease in birds and, when administered to chicks, elicited protection against challenge with a wild type virulent strain of S. Gallinarum (Figure 2). Vaccines based on these strains should be relatively inexpensive to manufacture and can be orally administered (i.e. needle-free) to young chicks or older birds by farmers. The vaccine is designed to prevent colonization, illness and/or death caused by the poultry pathogens Salmonella Gallinarum (fowl typhoid) and Salmonella Pullorum (pullorum disease). We demonstrated that vaccinated birds were also resistant to colonization by the human pathogen Salmonella Enteritidis. These results show that our candidate vaccine strains can protect chickens from fowl typhoid and may also reduce or prevent transmission of human pathogenic Salmonella strains. This oral, needle-free vaccine against fowl typhoid fulfills a need for an inexpensive and convenient means to enhance poultry production and improve poultry health.
