The roles of latency-associated antigens in tuberculosis vaccines

Abstract

Tuberculosis (TB) is a re-emerging disease and is caused by Mycobacterium tuberculosis (M. tuberculosis). TB is currently one of the leading causes of morbidity and mortality, worldwide. The only available vaccine against TB infection, Bacillus Calmette–Guérin (BCG), fails to adequately protect against reactivation of latent infections in adults. Furthermore, recently developed subunit vaccines, which are in various stages of clinical trials, are all prophylactic vaccines based on proteins expressed in replicating stage of M. tuberculosis and they are not preventive of reactivation of latent TB infection. Thus, an appropriate subunit post-exposure vaccine needs to be developed to control all forms of TB infection. To produce a multi-stage subunit vaccine, scientists should combine the early secreted M. tuberculosis antigens with latency antigens. For this purpose, some latency proteins are known which could be important antigens in the production of specific humoral and cellular immune responses in latent M. tuberculosis infected individuals. Several studies have evaluated the immunogenicity of these proteins in improving the TB vaccines. The present study is a comprehensive review of several studies on the role of the latency antigens in the development of TB vaccines. Overall, the studies indicate that the latency-associated antigens including the resuscitation-promoting factors, the Dormancy of survival regulon (DosR) proteins and the starvation stimulant proteins are potential candidates for the development of subunit vaccines against TB infection.