Grant: Project Grant

This research aims to further develop vaccines for flu and whooping cough. These diseases affect the very young, the elderly and anyone with a poor immune system most severely, even causing death. Yet those at most risk may not be able to take current vaccines. Changing the route of administration to intranasal, and avoiding live influenza virus will expand the range of those who can be vaccinated as well as generating a more effective immune response (both mucosal and systemic). Early stage research has already established an effective vaccine helper (adjuvant) for both of these diseases and the proposed formulations will make the vaccine work well by the nasal route. This route of administration will serve to improve the type and quality of immune response for these diseases in addition to being less invasive than an injection. The key to the new adjuvant for nasal administration is a formulation based on lipids, which bind to the adjuvant and help it reach the immune cells. Prior work shows the lipid-based adjuvant works well in animals using a model peptide intranasal vaccine. The proposed research will combine the new adjuvant formulations with either inactivated flu virus or with peptides from the whooping cough bacteria (antigens), followed by intranasal administration of the vaccine to mice and pigs. Cellular uptake, biodistribution and tissue gene expression responses will be measured to determine how the lipids improve the adjuvant's activity. Outcomes will include evaluating the immune response to the flu virus or to the whooping cough bacteria, such as antibodies raised and other immune responses. We will also look at how the animals respond to a challenge with the infectious agent after vaccination, such as whether they get sick and how much antibodies they make. The health of the nasal tissue and toxicity will be evaluated as well. In the case of whooping cough we will also evaluate the longer-term response to infection challenge after vaccination.