The current status, challenges, and future developments of new tuberculosis vaccines

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Abstract

Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10 causes of death worldwide. TB results in more fatalities than multi-drug resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the prevention and control of infectious diseases. Unfortunately, the only licensed preventive vaccine against TB, bacilli Calmette-Guérin (BCG), is ineffective for prevention of pulmonary TB in adults. Therefore, it is very important to develop novel vaccines for TB prevention and control. This literature review provides an overview of the innate and adaptive immune response during M. tuberculosis infection, and presents current developments and challenges to novel TB vaccines. A comprehensive understanding of vaccines in preclinical and clinical studies provides extensive insight for the development of safer and more efficient vaccines, and may inspire new ideas for TB prevention and treatment.

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Most cited references 165

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Immunometabolic Pathways in BCG-Induced Trained Immunity

Rob Arts, Agostinho Carvalho, Claudia La Rocca … (2016)

Summary The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.

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Who puts the tubercle in tuberculosis?

David Russell (2007)

Tuberculosis (TB), an illness that mainly affects the respiratory system, is one of the world's most pernicious diseases. TB currently infects one-third of the world's population and kills approximately 1.7 million people each year. Most infected individuals fail to progress to full-blown disease because the TB bacilli are 'walled off' by the immune system inside a tissue nodule known as a granuloma. The granuloma's primary function is one of containment and it prevents the dissemination of the mycobacteria. But what is the role of the TB bacillus in the progression of the granuloma? This Review explores how Mycobacterium tuberculosis influences granuloma formation and maintenance, and ensures the spread of the disease.

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Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis.

Laleh Majlessi, Jeffrey K Griffiths, Claude Leclerc … (2003)

The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG::RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.

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Author and article information

Journal

Title: Human Vaccines & Immunotherapeutics

Abbreviated Title: Human Vaccines & Immunotherapeutics

Publisher: Informa UK Limited

ISSN (Print): 2164-5515

ISSN (Electronic): 2164-554X

Publication date Created: June 20 2018

Publication date Created: July 03 2018

Publication date (Electronic): May 14 2018

Publication date (Print): July 03 2018

Volume: 14

Issue: 7

Pages: 1697-1716

Affiliations

[1 ] Army Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, Haidian District, Beijing, China

Article

DOI: 10.1080/21645515.2018.1458806

PMC ID: 6067889

PubMed ID: 29601253

SO-VID: 78cb58b0-90e5-4571-b254-c5ff103f8e79

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