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

ABSTRACT

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.

KEYWORDS:

• BCG
• DosR antigens
• latent tuberculosis
• reactivation
• Rpf proteins
• multistage vaccine
• murine LTBI models
• LTBI in non-human primates

Article highlights

• Only very recently has the role of BCG against reactivation from latent-like tuberculosis infection (LTBI) started to be analyzed.

• Currently, small (mouse) models using oral corticosteroids or antibiotic treatment followed by their deprivation are used to mimic reactivation from LTBI-like disease.

• A number of subunit vaccine candidates have been used to boost immunity provided by BCG as a means to control active or chronic TB.

• Vaccination using DosR-regulon or Rpf proteins, either by themselves or in combination with BCG might result in increased protection against LTBI or reactivation from it.

• Improvements to standard BCG include fusion proteins (partial or complete) as boosting schemes, expression of antigenic proteins in recombinant vaccine strains, and boosts with infection phase antigen mixtures with synthetic adjuvants.

• Immunity against latent infection is being deciphered in preclinical non-human primate models with insights on disease reactivation with scarce data on vaccine therapeutics against the dormant state of M. tuberculosis.

Acknowledgments

The authors like to thank both Mr. Ean Hundley and Mr. Brian Walsh from the U.S. Peace Corps for their helpful comments and review of this manuscript. The authors would like to apologize to all the authors whose important work was not included.

Declaration of interest

A H Alverez and M A Flores-Valdez are members of the Medical and Pharmaceutical Biotechnology group of a non-profit research center part of the Mexican Council of Science and Technology (CONACyT, Mexico). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The present work did not receive any kind of funding to declare.