Abstract: Vaccines comprising Mycobacterium tuberculosis (M. tuberculosis) PknD sensor polypeptides, compositions, kits, and methods of use for treating central nervous system tuberculosis are disclosed. More specifically, the disclosure provides a method for treating or preventing central nervous system (CNS) tuberculosis (TB) in a subject, the method comprises administering to the subject a therapeutically effective amount of a vaccine comprising an M tuberculosis PknD sensor polypeptide, or an immunogenic fragment for inhibiting or preventing M tuberculosis bacterial invasion of brain microvascular endothelia.