Characterizing the role of the HspX protein from Mycobacterium tuberculosis as a subunit vaccine candidate in the small animal model of tuberculosis

Abstract

Tuberculosis (TB) is a bacterial disease of the lung, caused by Mycobacterium tuberculosis, and currently remains an important human pathogen. The only vaccine against tuberculosis licensed for human use is a live, attenuated strain of the closely related Mycobacterium bovis Bacille-Calmette Guerin (BCG), which offers little protection against pulmonary disease in adults, particularly against latent infection. Current vaccine strategies against TB include the development of subunit vaccines, which contain one to a few antigens. Subunit vaccines are delivered with an adjuvant formulation to mount an appropriate T cell response against the pathogen. One such antigen for vaccine design is the 16kDa small heat shock protein and molecular chaperone from Mtb, HspX. This protein has been implicated as a latency-associated antigen due its late expression and ability to re-stimulate T cells from latently infected patients. A previous study in our laboratory revealed that native HspX purified from Mtb was protective in mice against pulmonary TB when given as a vaccine. HspX expressed and purified from E coli in its recombinant form was not able to protect. We hypothesize that because HspX functions as a molecular chaperone, it requires its binding partners to remain biologically active as a vaccine. In this study, we test this hypothesis and we also tested the capacity of native HspX to protect guinea pigs experimentally infected with TB. Our results illustrate that, while native HspX protects in the mouse model, it does not confer protection in guinea pigs, suggesting differences in the establishment of Mtb physiologically in the lung.