Journal of internal medicine
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Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving 'End TB' prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. ⋯ For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need.
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In recent years, the century-old Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been re-evaluated for its capacity to stem the global tide of TB. There is increasing evidence that the efficacy of BCG can be improved by the modified administration methods and schedules. Here, we first discuss recent approaches of vaccine administration, revaccination or boosting that have been used to try to improve the efficacy of BCG against TB. ⋯ These studies all highlight that there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity, which has been surprisingly understudied. We argue that several critical gaps in knowledge exist and must be addressed by future research to rationally improve the efficacy of BCG, including comprehensive, proteome-wide understanding of the epitopes derived from BCG recognized by BCG-vaccinated individuals, the phenotype of responding antigen-specific T cells and how previous exposure to environmental mycobacteria affect these parameters and thus influence vaccine efficacy. The development of modern techniques allows us to answer some of these questions to better understand how BCG works in terms of both protection against TB and the immune response that it triggers.
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Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is recommended at birth in TB-endemic areas. Currently, BCG vaccination programmes use "BCG vaccination coverage by 12 months of age" as the performance indicator. Previous studies suggest that BCG-vaccinated children, who develop a scar, have better overall survival compared with BCG-vaccinated children, who do not develop a scar. ⋯ Confounding and genetic factors are unlikely to explain the strong association between BCG scarring and subsequent survival. Including "BCG scar prevalence" as a BCG vaccination programme performance indicator should be considered. The effect of revaccinating scar-negative children should be studied.
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The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. ⋯ In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.