Targeting HspX of Mycobacterium tuberculosis: Advances in diagnostics, treatment, and vaccine development

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), Bacille Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis, but it provides limited and inconsistent protection against pulmonary TB in adults. Furthermore, current diagnostic methods show low sensitivity in latent stages, and the standard treatment is long, complex, and conducive to the emergence of drug-resistant strains. In this context, heat shock protein X (HspX), also known as Rv2031c or α-crystallin, has emerged as a potential biomarker and vaccine candidate. This 16-kDa protein is predominantly expressed under stressful conditions such as hypoxia and nitric oxide exposure, which are characteristic of the granulomatous microenvironment where MTB persists. Its expression during latency and high immunogenicity has been demonstrated in individuals with latent tuberculosis infection and those vaccinated with BCG. Preclinical studies have shown that recombinant HspX potentiates the host immune response used as a component in subunit vaccines, either alone or in combination with other antigens. Incorporating this protein into new diagnostic, therapeutic, and vaccine strategies could optimize disease control. This review explores HspX's multifaceted role and potential applications in tuberculosis diagnosis, treatment, and vaccine development.