Grant: Project Grant

Annual vaccines to influenza help reduce the spread and severity of flu, but effective protection depends on the generation of long-lived immune memory. Immune memory is established by many types of immune cells, including memory B cells, which can be recalled to produce protective antibodies that neutralize or block a recurring infection. Vaccination can establish pathogen-specific memory B cells without causing severe illness to establish this immune memory. However, despite the availability of vaccines, influenza is still a highly contagious virus that causes over 3,500 deaths in Canada each year. In addition to the limited duration of protection by influenza vaccines, some vaccine recipients fail to develop sufficient immune memory, and can develop severe disease. An immune signaling molecule called thymic stromal lymphopoietin (TSLP) acts on several different immune cells to modulate antibody production during inflammation. However, the role of TSLP and signaling by its receptor in regulating vaccine-induced immune memory has not yet been explored. In this study, we will investigate how TSLP receptor signaling modulates memory B cells after vaccination, and how TSLP signaling can be manipulated to modulate the establishment and recall ability of antigen-specific memory B cells. We hypothesize that TSLP signaling regulates both the generation and recall of memory B cells. This work has potential to help design better influenza vaccines that provide more potent or longer lasting protection. Furthermore, our findings could improve our understanding of TSLP and predict how TSLP targeted therapeutics could impact B cell responses.