Thesis Format
Integrated Article
Degree
Doctor of Philosophy
Program
Biology
Supervisor
Menassa, Rima
Affiliation
London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON
2nd Supervisor
Hill, Kathleen A.
Co-Supervisor
Abstract
Salmonella enterica serovars are major pathogens responsible for bacterial gastroenteritis in humans, primarily associated with poultry products. Controlling Salmonella in chickens is particularly challenging because infected birds often carry the pathogen undetected into slaughterhouses, leading to meat contamination. This issue is exacerbated by the rise of antibiotic-resistant strains, highlighting the need for alternative strategies, such as vaccines, to manage Salmonella infections and protect poultry health and food safety.
In this study, bacterial outer membrane proteins, were investigated as antigenic candidates for vaccine development. These proteins were produced in transplastomic plants to explore their potential as immunogens. Although the protein yield was insufficient for direct vaccine application, partially purified proteins elicited an immune response in mice, resulting in the production of antibodies capable of binding to Salmonella. The findings demonstrated the feasibility of using plant systems to produce complex bacterial proteins capable of stimulating an immune response.
Building on these findings, nanoparticle-based vaccine candidates were developed by fusing antigenic peptides from the same bacterial proteins with a self-assembling nanoparticle scaffold. These constructs were transiently expressed in plants, purified, and evaluated for their ability to elicit immune responses, demonstrating promising results in mice.
This research presents a novel approach to developing plant-based, nanoparticle vaccines, with potential applications in preventing Salmonella colonization in poultry, thereby contributing to improved animal health and food safety.
Summary for Lay Audience
Salmonella infection is an illness caused by a type of bacteria that mainly affects the stomach and intestines. This infection often comes from eating poultry products like chicken and eggs. It causes problems not just for people's health but also for the poultry industry, leading to losses in productivity and significant economic issues. One common way to control this disease is by adding antibiotics to animal feed. However, some types of Salmonella have become resistant to antibiotics, which makes this method less effective. Because of this, scientists are exploring new ways to fight the infection, such as developing vaccines. One promising approach to develop vaccines, especially for animals, is plant molecular farming. Plant molecular farming involves using plants to produce important biological substances, like vaccines. It is a cost-effective, safe, and easy-to-scale-up method. Several plant-based products, such as Elelyso (a treatment for Gaucher disease), are currently available on the market. The plant-based COVID-19 vaccine developed by Medicago, named Covifenz, received approval from Health Canada in February 2022. Additional products are anticipated to emerge in the coming years.
The main goal of this project was to see if we could use plants to develop a vaccine to protect chickens from Salmonella infection. The focus was on using specific proteins found in the bacteria's outer membrane. The project started by trying to produce these proteins in the chloroplasts (the part of the plant cell where photosynthesis happens) of tobacco plants. After extracting these proteins, we found that they could trigger an immune response in mice, causing the mice to produce antibodies that target Salmonella. Although the amount of protein produced was too low to use as a vaccine, this experiment showed that it is possible to produce complex proteins in plant chloroplasts. Next, we created a plant-based nanoparticle vaccine using these proteins. A nanoparticle vaccine is a type of vaccine where small particles (nanoparticles) are used to carry the vaccine ingredients, making it easier for the immune system to recognize and respond to them. These proteins were produced in a wild relative of tobacco. After extracting and purifying the proteins, we tested them in mice. The results were promising. The vaccine candidates caused the mice to produce specific antibodies that could attach to the surface of Salmonella. This suggests that our plant-based vaccine candidates could potentially prevent Salmonella infections in poultry, although more research and development are needed.
Recommended Citation
Shamriz, Shabnam, "Engineering Plant-Produced Nanoparticle Vaccines Targeting Salmonella Colonization in Poultry" (2024). Electronic Thesis and Dissertation Repository. 10592.
https://ir.lib.uwo.ca/etd/10592
