Targeting lung tissue resident immunity via intramuscular vaccination for protection against Mycobacterium tuberculosis 2300551

Abstract

Abstract Introduction An improved tuberculosis (Tb) vaccine is needed to confer long lasting protection for all individuals targeting correlates of protection (CoP). We seek to generate a parenterally administered vaccine that induces strong lung-resident immune responses to protect against Mtb. Methods We hypothesize that intramuscular (IM) vaccination with adjuvant double mutant Escherichia coli heat-labile toxin (dmLT) and a bacterial OMV-derived adjuvant (T-vant) will induce a robust response, driving tissue resident immunity in the lung. Mice will be vaccinated IM with antigen alone or antigen with the cocktail in a prime-boost fashion. Two weeks post boost, mice will be intravenously injected with CD45 antibody to differentiate circulating vs non-circulating tissue resident cells. Lymph nodes, spleens, and lungs will be stained with antigen-specific MHCII tetramer to identify CD4+ T cells that are vaccine-specific. Flow cytometry will identify cells that are tissue resident (IV CD45-CD69+P2X7R+), and serum and BAL fluid will be collected for antibody titers. Results In comparison to other routes, IM vaccination generated the highest number of vaccine specific CD4+ and CD8+ T cells. Following IM immunization, we observed significantly higher numbers of tissue resident vaccine-specific CD4+ in the lung of adjuvant vaccinated mice than naïve or antigen alone groups. These cells preferentially displayed a TH1/TH17 phenotype, which are key correlates of protection for Mtb infection. Conclusion These findings suggest that our combination adjuvanted vaccine might produces lung-resident immune responses that could provide increased protection against lung infections. We hope to utilize this in developing novel vaccines for Tb that target CoPs for lasting protection for all individuals. Funding Source NIH Topic Categories Mucosal and Regional Immunology (MUC)