Development and characterization of a broadly-protective mucosal vaccine for highly-pathogenic avian influenza H5N1

Influenza viruses have caused multiple global pandemics over the past century and continue to pose a serious threat to human health. Highly pathogenic avian influenza (H5N1), has recently spread widely in birds and other animals. Since 2024, it also been detected in dairy cattle in the U.S. This virus has caused human infections in both the United States and Canada, raising concerns about its pandemic potential. Current influenza vaccines are given by injection and fail to generate strong immune responses in the lungs, where severe influenza causes the most damage. They also tend to work best only against closely matched strains, limiting their usefulness against new, emerging viruses like H5N1. Our team has developed a new type of vaccine that is delivered directly to the airways. This approach is designed to build strong immunity in the lungs-the main site of serious influenza disease-and to provide broader, longer-lasting protection. We have already shown that this vaccine platform works well against COVID-19 and is safe in people. In this project, we will adapt this technology to create a next-generation vaccine against H5N1 influenza. We will test whether this vaccine can safely trigger strong immune defenses in the lungs, protect against severe disease, and defend against different strains of influenza in animal models. We will also study how the vaccine works, including the roles of antibodies, immune cells, and the body's early "first-line" defenses. This research aims to lay the groundwork for a more effective, broadly protective influenza vaccine to help Canada and the world prepare for future influenza pandemics.