What
Transmission of respiratory viruses is a highly current topic with the ongoing SARS-CoV2 pandemic. However, how the immune cells impacts transmission remains largely uninvestigated. I'm interested in understanding how cellular immunity can contribute to limit virus transmission and thereby improve herd immunity. CD8 T cells can recognize parts of viruses that are highly conserved between strains and because of this, memory CD8 T cells are able to protect individuals where antibody-mediated immunity fails due to a mismatch between antibody and virus. Specifically, tissue resident CD8 T cells in the lungs and airways are indispensable for optimal protection against respiratory viruses and I therefore want to investigate if and how these cells can also limit transmission of respiratory virus.
Why
Viruses are continuously changing by mutations, which may lead to inefficient recognition and neutralization by antibodies generated by vaccines. As an increasing number of studies over the last decade have underscored the possibilities of CD8 T cell immunity, research is being aimed at developing a T cell based vaccine. It is important to note that T cell immunity is not per se a sterilizing immunity, and it therefore needs to be investigated if it will contribute to limit, or even prevent any occurrence of viral transmission. To make informed decisions on vaccine design, we need to understand multiple components of the immune system and how they contribute to protecting vaccinated individuals, but also the large population.
How
One of the reasons this hasn't been studied before, is because the lack of a good animal model as influenza viruses doesn't transmit in mice. To solve this, I will work with a natural mouse parainfluenza virus, Sendai virus that readily transmits via the aerosol and contact routes. Using Sendai virus expressing luciferase will allow me to collect longitudinal data using in vivo imaging to non-invasively measure virus and transmission in infected mice. Further, I will use recombinant influenza virus and adenovirus expressing the immunodominant Sendai nucleoprotein CD8 T cell epitope. This will allow generation of tissue resident memory CD8 T cells, without having any other Sendai specific immunity.
SSR
The ongoing pandemic has clearly emphasized the need to understand multiple components of immunity to respiratory viruses. Often, the majority of focus is being put on understanding antibody mediated immunity, but with forever mutating viruses it is critical to also consider other branches of the immune system. The benefit of CD8 T cell immunity is that it is mainly targeting highly conserved internal parts of viruses. To fully evaluate and recognize the importance of CD8 T cell immunity, it is critical to understand if and how respiratory tissue resident memory CD8 T cells influence transmission of viruses. This project will provide us with information about parameters to consider for vaccine design in the future, ideally utilizing aid from multiple arms of the immune system, giving us the best protection possible.