Tissue-resident memory T-cells (TRM) in the airways can be induced by primary viral infections or as a response to mucosal vaccination. Intranasal applications of adenoviral vectors resulted in high frequencies of nucleoprotein (NP)-specific TRM, which could provide a heterosubtypic immunity against various Influenza A Virus (IAV) strains.
Dendritic cells (DC) are crucial for the induction of TRMs in the lung, however the effect of individual DC subtypes remains unclear. Therefore, the first aim is to examine the impact of cDC1 in the induction of a TRM response after an intranasal adenoviral vector immunization. By comparing the immune response of BATF3-/- k.o. mice lacking cDC1 in the lung to WT animals, we will analyze the impact of this DC subtype on the TRM formation.
The second aim is to apply the method of specific DC-targeting through endocytic surface receptors of dendritic cells to an adenoviral vector immunization. In contrast to the previously mentioned protein-based vaccines with the antibodies used by the Dudziak laboratory, we are going to produce an adenoviral vector encoding a single chain antibody fragment (scFv) against DC surface receptors fused to the antigen NP. An intranasal immunization with the adenoviral vector vaccine could have an impact on the TRM numbers in the mucosal airways. We want to compare whether specific DC-targeting through an adenoviral vector vaccine can improve the TRM response. The results will lead to a better understanding of the role of DCs during the TRM formation and will guide further vaccine development.
