BACKGROUND:Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb).This disease with two million deaths per year has the highest mortality rate among bacterial infections.The only available vaccine against TB is BCG vaccine.BCG is an effective vaccine against TB in childhood,however,due to some limitations,has not proper efficiency in adults.Also,BCG cannot produce an adequately protective response against reactivation of latent infections.OBJECTIVE:In the present study we will review the most recent findings about contribution of HspX protein in the vaccines against tuberculosis.METHODS:Therefore,many attempts have been made to improve BCG or to find its replacement.Most of the subunit vaccines for TB in various phases of clinical trials were constructed as prophylactic vaccines using Mtb proteins expressed in the replicating stage.These vaccines might prevent active TB but not reactivation of latent tuberculosis infection (LTBI).A literature search was performed on various online databases (PubMed,Scopus,and Google Scholar) regarding the roles of HspX protein in tuberculosis vaccines.RESULTS:Ideal subunit post-exposure vaccines should target all forms of TB infection,including active symptomatic and dormant (latent) asymptomatic forms.Among these subunit vaccines,HspX is the most important latent phase antigen of M.tuberculosis with a strong immunological response.There are many studies that have evaluated the immunogenicity of this protein to improve TB vaccine.CONCLUSION:According to the studies,HspX protein is a good candidate for development of subunit vaccines against TB infection.