Adjuvanted Intranasal Influenza Vaccine to Generate Lung Resident-Memory T Cells

ABSTRACT Influenza vaccine capable of providing broadly cross-reactive and heterosubtypic Immunity (HSI) is a strategic solution to overcome the uncertainties associated with annual influenza immunizations. Lung resident memory CD8 T cells are important players in heterosubtypic immunity and protection after influenza infections. Current vaccine technologies used in influenza vaccines are not very effective in generating lung resident T cell memory, with the exception of live attenuated influenza vaccines (LAIV). We have recently demonstrated an enantiomer specific 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as immune stimulatory cationic lipid (CL), which can adjuvant intramuscularly administered recombinant proteins to generate robust cellular and antibody mediated response. In preliminary studies, we observed this CL can also induce potent immune responses when administered intranasally. In this proposal, we will characterize T cell-mediated immune responses to R-DOTAP adjuvanted influenza vaccines delivered as an intranasal formulation with emphasis on its ability to generate tissue-resident memory CD8 T cells and provide protective and cross-reactive CD8 T cell immunity to an infection challenge. In the first specific aim we will evaluate lung-resident memory T cell induction by intranasal R-DOAP adjuvanted recombinant protein vaccine. In the second specific aim, we will evaluate the vaccines efficacy to protect mice from a heterosubtypic Influenza A challenge. A thorough characterization of R-DOTAP’s ability to induce lung resident T cells will be useful for the adjuvant development field and contribute to the development of effective next-generation vaccines.