Can immunization with Bacillus Calmette-Guérin be improved for prevention or therapy and elimination of chronic Mycobacterium tuberculosis infection?

Introduction: Tuberculosis (TB) is one of the most prevalent infectious diseases in the world. Current vaccination with BCG can prevent meningeal and disseminated TB in children. However, success against latent pulmonary TB infection (LTBI) or its reactivation is limited. Evidence suggests that there may be means to improve the efficacy of BCG raising the possibility of developing new vaccine candidates against LTBI.Areas covered: BCG improvements include the use of purified mycobacterial immunogenic proteins, either from an active or dormant state, as well as expressing those proteins from recombinant BCG strains that harvor those specific genes. It also includes boost protein mixtures with synthetic adjuvants or within liposomes, as a way to increase a protective immune response during chronic TB produced in laboratory animal models. References cited were chosen from PubMed searches.Expertopinion: Strategies aiming to improve or boost BCG have been receiving increased attention. With the advent of -omics, it has been possible to dissect several specific stages during mycobacterial infection. Recent experimental models of disease, diagnostic and immunological data obtained from individual M. tuberculosis antigens could introduce promising developments for more effective TB vaccines that may contribute to eliminating the hidden (latent) form of this infectious disease.

Expression of non-replicating persistence associated genes of Mycobacterium bovis in lymph nodes from skin test-reactor cattle.

Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. It remains unclear whether expression of NRP genes occurs within the tissue of Mycobacterium bovis naturally infected cattle. In order to start dissecting this question, total RNA from bovine lymph node tissues of sacrificed tuberculin reacting animals was isolated and transcription of genes required for in vivo duplication (esxB and fbpB) and in vitro NRP (hspX, pfkB, and mb2660c) were analyzed by RT-PCR approaches. Detection of transcripts was positive in bovine tissue samples for genes hspX, pfkB, and mb2660c in 84, 32, and 21%, respectively. NRP genes were upregulated even in animals with a negative IFN-γ in vitro test, and the expression of NRP genes occurred more often than expression of the esxB gene.

Vaccination of mice with recombinant bacille Calmette-Guérin harboring Rv1357c protects similarly to native BCG.

Despite the availability of a Mycobacterium bovis bacille Calmette Guérin (BCG) vaccine, tuberculosis (TB) remains a global public health problem. In this study, we introduced the c-di-GMP phosphodiesterase gene Rv1357c, implicated in regulating mycobacterial replication within macrophages, into BCG Pasteur, and tested the resulting strain for its capacity to serve as a vaccine against TB in a murine model. Modified BCG was more phagocytosed than its parental strain, but halted bacterial replication, and protected against M. tuberculosis challenge similarly to unmodified BCG.