Induction of tissue-resident memory T cells by gene-based vaccines as first line of defence against pathogens entering the host via mucosal surfaces
Vaccines are the most effective way of controlling influenza infection. However, the antibody response produced upon immunization is limited to the strains used to formulate the vaccine, therefore an annual reformulation is necessary due to the high mutation rate of the viruses. There is an urgent need to find a new vaccine, which is able to mount a heterologous response. Several studies in humans and animal models have shown that T cells, more specifically tissue resident memory (TRM) T cells, are more efficient to promote heterologous protection in the context of influenza. These non-circulating T cells are able to provide protection against different influenza strains. However, these cells have a short life, being only maintained due to the inflammatory processes occurring in the lung during infection. Recently, we showed that mucosal administration of IL-1β promoted the formation of TRM cells, which was sufficient to control viral replication of heterologous strains in the lung of mice. Moreover, IL-1β administration led to an increase of inflammation that is known to be harmful for the lung. This proposal grant aims to generate and study the immunogenicity of new adjuvants to replace IL-1β, but also understand in depth the role of this cytokine on TRM development. Understanding the role of IL-1β signalling will provide us new insights on TRM differentiation, which consequently will allow us to find a new and less harmful adjuvant to use together with vaccination.
