January 16, 2020

Drs. Vladimir Badovinac and John Harty have successfully renewed their R01 grant entitled ‘Memory CD8 T Cell Localization and Protection from Influenza’ from the National Institute of Allergy and Infectious Diseases (NIAID). Drs. Badovinac and Harty are Co-Principle Investigators on the project.

Influenza infection is a recurring public health burden and our current strategies of seasonal influenza vaccination provide suboptimal protection. Thus, it is critical to provide basic, mechanistic insights into the possibility of universal influenza vaccines and much work so far is devoted to strategies to induce broadly neutralizing antibodies. However, in the absence of neutralizing antibodies, the presence of IAV-specific memory CD8 T cells targeting conserved viral proteins such as NP or M2, which are maintained systemically as well as in the lung correlate with control of viral titers and reduction of disease symptoms in humans. Mouse models suggest it is the lung resident memory CD8 T cells (Trm) that enable swift and robust protection against IAV infection. Thus, establishing a robust long-term Trm population in the lung may be an important goal for an IAV vaccine with broad coverage. Recent evidence from our laboratories shows that repetitive encounter with influenza infection to generate quaternary memory in the lung profoundly improves the durability of lung Trm and heterosubtypic immunity compared to primary memory Trm. Thus, our long-term goal in the next five years will be to understand the biology of IAV-induced Trm and how these cells can be manipulated to enhance immunity to aid in development of universal influenza vaccines.