BCG vaccine — Is tuberculosis still a threat?

Aim of the study: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood.

Results: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect.

Aim of the study: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies.

Results: The protective effect of the first dose of the BCG vaccine against tuberculosis in its miliary and meningeal forms is high. However, the results vary in relation to the pulmonary form of the disease, with some indicating zero effect and others levels of nearly 80%. Research is being carried out to develop new vaccines that could substitute the BCG or be used as a booster. There are evidences that the protective effect of the BCG vaccine does not increase with a second dose. In spite of its limitations and the expectation that a new tuberculosis vaccine will be developed in the future, the BCG vaccine remains an important tool in controlling the harmful effects of tuberculosis, particularly in countries with medium or high incidence levels of the disease.

Aim of the study: 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.

Results: Critical research priorities for M72/AS01E include completing the currently in-design trial, powered to improve the precision of efficacy estimates, include uninfected populations and further assess safety and immunogenicity in HIV-infected people. 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.

Aim of the study: Tuberculosis (TB) is the leading cause of death worldwide due to an infectious disease, causing around 1.6 million deaths each year. This situation has become more complicated by the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) and HIV-TB co-infection, which has significantly worsened TB prognosis and treatment.

Results: Despite years of intensive research, Bacille Calmette-Guerin (BCG) remains the only licensed vaccine and has variable efficacy. It provides protection against childhood TB but is not effective in adult pulmonary TB. As a result of intense research in understanding TB vaccinology, there are many new vaccine candidates in clinical development and many more in pre-clinical trials which aim either to replace or boost BCG vaccine. This review discusses the history of BCG vaccine development and summarizes limitations of the current vaccine strategy and recent advances in improving BCG immunization along with other new vaccines in clinical trials which are promising candidates for the future tuberculosis vaccinology program.

Aim of the study: Tuberculosis infects millions of people worldwide and remains a leading global killer despite widespread neonatal administration of the tuberculosis vaccine, bacillus Calmette-Guérin (BCG). BCG has clear and sustained efficacy, but after 10 years, its efficacy appears to wane, at least in some populations.

Results: Here we review the epidemiological need for tuberculosis vaccination, including evolving standards for administration to at risk individuals in developing countries. We also examine proven sources of immune protection from tuberculosis, which to date have exclusively involved natural or vaccine exposure to whole cell mycobacteria. After summarizing evidence for the use and efficacy of BCG, we detail the most promising new candidate vaccines against tuberculosis. The global need for a new tuberculosis vaccine is acute and huge, but clinical trials to be completed in the coming few years are likely either to identify a new tuberculosis vaccine or to substantially reframe how we understand immune protection from this historical scourge.

Aim of the study: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, particularly in low- and middle-income countries. The Bacillus Calmette-Guérin (BCG) vaccine, developed from attenuated Mycobacterium bovis (M.

Results: While adverse effects are generally mild, they tend to be more pronounced in immunocompromised individuals. This review examines the historical development, biotechnological production, immunological mechanisms, and expanding therapeutic applications of BCG. We synthesized findings on strain variability, manufacturing processes, and immune responses, highlighting the induction of T helper 1 (Th1)-mediated cellular immunity through interferon gamma (IFN-γ) and interleukin-12 (IL-12), macrophage activation, and granuloma formation. Overall, BCG represents both a critical public health intervention and a model system for advancing immune-based therapies.

Aim of the study: The genetic diversity of Mycobacterium tuberculosis challenges Tuberculosis control and may contribute to variable protection by BCG. We evaluated pathogenesis and BCG efficacy against clinical Kenyan Mtb isolates grouped by epidemiological transmissibility.

Results: Splenic control differed by host: CB6F1 mice showed reduced dissemination at 12 weeks, whereas C57BL/6 mice showed limited systemic control. Dissemination kinetics also differed, with early splenic spread of T2 and delayed dissemination of CAS1-Kili. Notably, BCG consistently reduced lung pathology even when bacterial burden reductions were modest. Overall, BCG efficacy was strain-, host-, organ- and time-dependent, underscoring the need for durable vaccines protective across diverse lineages.