A MAPS Vaccine Induces Multipronged Systemic and Tissue- Resident Cellular Responses and Protects Mice against Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. To date, themainstay of vaccination involves the use ofMycobacteriumbovis bacillus Calmette-Guérin (BCG), a live-attenuated vaccine that confers protection against extrapulmonary disease in infants and children but not against lung disease. Thus, there is an urgent need for novel vaccines. Here, we show that a multicomponent acellular vaccine (TB-MAPS) induces robust antibody responses and long-lived systemic and tissue-resident memory Th1, Th17, and cytotoxic CD41 and CD81 T cells, and promotes trained innate immunity mediated bygd T and NKT cells in mice. When tested in a mouse aerosol infection model, TB-MAPS significantly reduced bacterial loads in the lungs and spleens to the same extent as BCG. When used in conjunction with BCG, TB-MAPS further enhanced BCG-mediated protection, especially in the lungs, further supporting this construct as a promising TB vaccine candidate.