Matthew James Gagne

I am an assistant professor and a mucosal immunologist in the Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet. My research focus is on the optimization of intranasal vaccines for the prevention of respiratory virus infections.

My Question: Why did the COVID-19 pandemic persist for years after the widespread availability of vaccines? Why do flu vaccines fail to provide life-long immunity? Will there be another pandemic? The fact that we are asking these questions demonstrates the limitations to our understanding of how to make a high quality vaccine for a respiratory virus. For decades, vaccine scientists have focused on the development of better quality vaccine antigens, which is the part of a vaccine that triggers a longterm memory response and mimics the real pathogen. However, that is only part of what is needed to make a good quality vaccine. Vaccines also require choices regarding platform (RNA or protein), delivery vehicle (lipid nanoparticle or viral vector), adjuvants and delivery route. It is this last item - delivery route - that I am particularly interested in.

The Answer: Rather than trying to make a better quality vaccine that we deliver to muscle tissue far away from the locations in the body where respiratory viruses replicate, we should focus on improvement of intranasal and aerosol vaccines that drive immune responses to the exact sites where respiratory viruses first enter the body. Through a combination of mucosal organoids and in vivo models, I am launching the M-ORPH project at Karolinska Institutet. M-ORPH is a research pipeline for the testing and validation of mucosal vaccine components including antigens and delivery vehicles to increase the likelihood of success in clinical trials. Instead of validating a vaccine against any one specific pathogen, this approach will allow us to create a template for the optimization of all potential mucosal vaccines and give us the tools necessary to understand the unique mechanisms involved in upper respiratory tract immunology. M-ORPH will prepare us for anything from seasonal flu infections and the common cold to bird flu or the inevitable next pandemic.