Provided herein are fusion polypeptides comprising at least two Mycobacterial antigens, wherein one Mycobacterial antigen is a strong central memory T cell activator, and wherein one Mycobacterial antigen is a strong effector memory T cell activator. Also provided herein are methods of making and using such fusion polypeptides for the prevention or treatment of a secondary Mycobacterium tuberculosis infection as well as for the prevention or treatment of a nontuberculous Mycobacterium infection in a mammal.