Investigating the spatial landscape of influenza-induced anti-viral immunity in the lung.

Influenza A virus (IAV) vaccination strategies and immunity generated from natural infection with IAV rarely provide long-lasting immunity. This is partly because the surface viral proteins that antibodies target are prone to change. Therefore, antibody-mediated protection against one IAV infection is not always protective against future variants. Thus, it is important to understand how the immune system can target conserved viral aspects that are shared between strains. There are two main strategies to generate generalised immunity and I will investigate the potential of both. Firstly, I will investigate how resident memory T-cells, a type of immune cell that stays in the lung post-infection and targets conserved IAV proteins are retained after infection. Using a modified IAV, I will look at how signals required for their retention are maintained. This may allow us to improve their retention and promote longer-lived protection. Secondly, I will investigate how IAV infection causes a window of non-specific anti-viral immunity. Using novel mouse models, I will interrogate which immune cells control this behaviour and how they do this. Moreover, I want to know whether the antiviral effect is limited to regions of the lung that have previously seen IAV infection and whether this can be boosted.