Grant: Project Grant

The flu is a lung disease caused by infection with the influenza virus. Flu infections are very common during the winter months and can cause death in vulnerable people such as the very young, the very old, and those with chronic diseases. One way to decrease deaths from the flu is to vaccinate people. Most vaccines are given by injection into muscles. The cost of these vaccines is high because they are expensive to produce and require medical personnel to administer. There is a lot of interest to develop vaccines that we can give into the nose because they are less painful, less expensive, easier to administer, and also more effective. The main problem with this approach is that the vaccines we give into the nose need to have an "adjuvant", a compound that will help stimulate our immune system to respond to the vaccine. Unfortunately, we do not have good adjuvants for nasal vaccines. We have identified a compound that has the potential to work as an adjuvant for a nasal flu vaccine. This compound is a small molecule that triggers a cell surface structure called Proteinase-Activated Receptor-2 (PAR-2). When we trigger PAR-2 the body produces chemicals that can activate our immune system. Our objective is to study the ability of this molecule (we call it PAR-2AP) to function as adjuvant for flu vaccination using mice. We will give mice a vaccine against flu alone or together with PAR-2AP. We will then measure the ability of their immune system to protect the mice in case they develop a flu infection. We will identify the best approach to give the vaccine with PAR-2AP to induce the highest level of protection and we will study the mechanisms that lead to protection from infection. This is the first time that this compound is studied for this ability as an adjuvant. The benefit of our approach is that this compound is easy to produce and inexpensive, and can be delivered into the nose so it will be easy to produce vaccines using this compound.