Characterizing signal 4 for CD8 T cell accumulation and memory formation during respiratory influenza virus infection

Every year a few thousand Canadians die of influenza virus (flu) infection. Occasionally, we have pandemics of influenza virus, which can cause much more loss of life, such as occurred in 1918 when a new strain of influenza infected 1/3 of the world and killed more than 50 million people. Although we now have vaccines to prevent influenza infection, the virus is constantly changing, and vaccines must be reformulated annually. The current vaccines are based on generating antibodies to prevent infection. However, if a virus bypasses those antibody defenses and gets into your cells, then those cells become factories to make more virus. To eliminate the infected cells an immune cell called a CD8 T cell is required. These so-called "Killer T cells" are important in eliminating the infected cells to clear the infection. After you recover from infection, some of the T cells remain in place to prevent reinfection, referred to as memory T cells. One useful feature of T cells is that they tend to recognize more conserved regions of the flu virus, compared to antibodies, which recognize parts of the virus that can rapidly change to escape the antibodies. If we induce a really strong T cell response to influenza in our vaccines, this could add a level of protection against multiple influenza strains, especially when combined in a vaccine that induces neutralizing antibodies to influenza virus. Using a mouse model of influenza virus infection, our proposal is aimed at understanding the key components of the immune response to influenza virus that result in strong T cell memory against influenza virus. This could lead to new strategies for designing vaccines to influenza virus. Our results will provide insights into what we need to measure to see that we have the correct immune response after vaccination. The information we gain from this study could also help us learn how best to vaccinate against other respiratory viruses, such as SARS-CoV-2 the virus that causes COVID19.