Intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis

Abstract Mucosal vaccines have the potential to elicit protective immune responses at point of entry respiratory pathogens thus preventing even initial seed infection. Unlike licensed injectable vaccines, mucosal comprising protein subunits are only in development stage. One primary challenges associated with has been identification and characterization safe yet effective adjuvants that can effectively prime multi-factorial immunity. In this study, we tested NanoSTING, a liposomal formulation endogenous activator stimulator interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as adjuvant. Intranasal administration vaccine provides protection comparable subcutaneous live attenuated Mycobacterium bovis strain Bacille–Calmette–Guérin (BCG) upon challenge aerosolized tuberculosis Erdman strain. Protection against bacterium is likely due CXCR3+ lung resident T cells known be important for control bacterial delivery also induces IFNγ secreting CD4+ which necessary intracellular bactericidal activity. Our results indicate NanoSTING adjuvanted response durable from infection by M. tuberculosis.