Exosomes carrying mycobacterial antigens can protect mice against <i><scp>M</scp>ycobacterium tuberculosis</i> infection

Abstract

Approximately 2 billion people are infected with M ycobacterium tuberculosis , the etiological agent of tuberculosis ( TB ), and an estimated 1.5 million individuals die annually from TB. Presently, M ycobacterium bovis BCG remains the only licensed TB vaccine; however, previous studies suggest its protective efficacy wanes over time and fails in preventing pulmonary TB . Therefore, a safe and effective vaccine is urgently required to replace BCG or boost BCG immunizations. Our previous studies revealed that mycobacterial proteins are released via exosomes from macrophages infected with M . tuberculosis or pulsed with M . tuberculosis culture filtrate proteins ( CFP ). In the present study, exosomes purified from macrophages treated with M . tuberculosis CFP were found to induce antigen‐specific IFN ‐γ and IL ‐2‐expressing CD 4 + and CD8 + T cells. In exosome‐vaccinated mice, there was a similar T H 1 immune response but a more limited T H 2 response compared to BCG ‐vaccinated mice. Using a low‐dose M . tuberculosis mouse aerosol infection model, exosomes from CFP ‐treated macrophages were found to both prime a protective immune response as well as boost prior BCG immunization. The protection was equal to or superior to BCG . In conclusion, our findings suggest that exosomes might serve as a novel cell‐free vaccine against an M . tuberculosis infection.