The adjuvant effects of rapamycin, metformin and aspirin on the T-cell immunological memory induced by tuberculosis subunit vaccine

The formation of long-lived T-cell immunological memory is a critical goal of vaccines against intracellular pathogens like Mycobacterium tuberculosis ( M. tuberculosis ). In this study, to verify the adjuvant effect of the metabolic regulator on T-cell memory induced by the tuberculosis subunit vaccine, we treated the mice with rapamycin, metformin and aspirin during the course of vaccination and then monitored the vaccine-specific long-term memory T cell responses and protective ability against mycobacterial organism. Compared with the mice that received the vaccine alone, rapamycin and metformin treatments enhanced the vaccine-specific long-term T-cell memory responses, and the potentiating effect of rapamycin is better than metformin. In particular, we found that a long duration of low-dose rapamycin treatment promoted the development of more T CM like cells and enhanced the vaccine’s long-term protective efficacy, which resulted in a better decline of 0.89-log10 CFU of mycobacterial organisms in lungs. These findings might have important implications for developing new vaccination strategies for the TB subunit vaccine.