Defining mechanisms of T cell help for pathogen-specific IgA responses at mucosal surfaces

Many viruses enter the body at mucosal surfaces such as the airways and gut. Once they get past these mucosal surfaces, they can cause significant harm - for example lung damage in the context of COVID-19. Vaccines do a good job at limiting this damage by provoking strong systemic immunity throughout the body. However these vaccines don't do a good job at placing immune cells at the mucosal surface itself. If we could learn how to do this, then we can prevent infections from happening in the first place. This would be a huge advantage as such vaccines would curb person-to-person transmission. One of the major molecules produced by the immune system at mucosal surfaces is antibodies of the IgA class. We and others have learned that IgA correlates with protection against SARS-CoV-2 infection, and the same has been found for gastrointestinal illnesses such as rotavirus. However, we do not fully understand how IgA against these viruses is induced. Filling this knowledge gap would allow us to design vaccines that have the potential to induce IgA at mucosal surfaces. Such vaccines would be tremendously helpful in congregant settings where person-to-person transmission is more likely. This CIHR project grant aims to better understand the signals that induce IgA to two viruses that infect the gut (rotavirus) and the upper respiratory tract (SARS-CoV-2).