Novel vaccination approaches to prevent tuberculosis in children.

James A Triccas,Claudio Counoupas

doi:10.1186/s41479-016-0020-z

James A Triccas, Claudio Counoupas

Open Access

https://doi.org/10.1186/s41479-016-0020-z

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Abstract

Pediatric tuberculosis (TB) is an underappreciated problem and accounts for 10 % of all TB deaths worldwide. Children are highly susceptible to infection with Mycobacterium tuberculosis and interrupting TB spread would require the development of effective strategies to control TB transmission in pediatric populations. The current vaccine for TB, M. bovis Bacille Calmette-Guérin (BCG), can afford some level of protection against TB meningitis and severe forms of disseminated TB in children; however, its efficacy against pulmonary TB is variable and the vaccine does not afford life-long protective immunity. For these reasons there is considerable interest in the development of new vaccines to control TB in children. Multiple vaccine strategies are being assessed and include recombinant forms of the existing BCG vaccine, protein or viral candidates designed to boost BCG-induced immunity, or live attenuated forms of M. tuberculosis. A number of these candidates have entered clinical trials; however, no vaccine has shown improved protective efficacy compared to BCG in humans. The current challenge is to identify the most suitable candidates to progress from early to late stage clinical trials, in order to deliver a vaccine that can control and hopefully eliminate the global threat of TB.

Highlights

Tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis, remains a major cause of mortality and morbidity worldwide
An additional Phase IIb trial assessing the efficacy in healthy adults infected with human immunodeficiency virus (HIV) in South Africa and Senegal demonstrated significant T-cell responses induced by the vaccine but there was no improved efficacy against M. tuberculosis infection or disease in the MVA85A group compared to placebo [37]
No vaccine has demonstrated improved protective efficacy in humans compared to the existing Bacille Calmette-Guérin (BCG) vaccine, and the immunological parameters required for effective protective efficacy in humans are not known

Summary

Introduction

Tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis, remains a major cause of mortality and morbidity worldwide. Numerous Phase II trials in adolescents [18], adults [19] or BCG-vaccinated infants [20] demonstrated the generation of polyfunctional CD4+ T-cells, augmented humoral responses and no adverse events associated with the vaccine. The vaccine was shown to retain immunogenicity in HIV+ subjects on anti-retroviral therapy [21] and has recently entered a Phase IIb proof of concept efficacy study in latently-infected adults (ClinicalTrials.gov Identifier: NCT01755598).

Results

Conclusion