100 years of Mycobacterium bovis bacille Calmette-Guérin

Abstract

Mycobacterium bovis bacille Calmette-Guérin (BCG), an experimental vaccine designed to protect cattle from bovine tuberculosis, was administered for the first time to a newborn baby in Paris in 1921. Over the past century, BCG has saved tens of millions of lives and has been given to more humans than any other vaccine. It remains the sole tuberculosis vaccine licensed for use in humans. BCG provides long-lasting strong protection against miliary and meningeal tuberculosis in children, but it is less effective for the prevention of pulmonary tuberculosis, especially in adults. Evidence mainly from the past two decades suggests that BCG has non-specific benefits against non-tuberculous infections in newborn babies and in older adults, and offers immunotherapeutic benefit in certain malignancies such as non-muscle invasive bladder cancer. However, as a live attenuated vaccine, BCG can cause localised or disseminated infections in immunocompromised hosts, which can also occur following intravesical installation of BCG for the treatment of bladder cancer. The legacy of BCG includes fundamental discoveries about tuberculosis-specific and non-specific immunity and the demonstration that tuberculosis is a vaccine-preventable disease, providing a foundation for new vaccines to hasten tuberculosis elimination.

Figure 1:. The founders of BCG

Jean-Marie Camille Guérin (1872–1961), left, and Léon Charles Albert Calmette (1863–1933), right.

Figure 2:. The unfolding of the BCG disaster in Lübeck in 1930

Note that three of the 251 infants were vaccinated before the start of the BCG campaign on Feb 24, 1930.

Figure 3:. Trained immunity induced by BCG

The accessibility of chromatin, in particular of promoters and enhancers, is modulated by BCG vaccination. Upon cellular activation of innate immune cells, histone chemical modifications (eg, methylation, acetylation) result in an increased accessibility for transcription factor binding and initiation of gene transcription. Upon elimination of the stimulus, many of these changes are lost,. But some histone marks (such as methylation) are preserved, bookmarking the genes important for host defense. Upon reinfection, chromatin architecture changes and induction of gene transcription can take place more quickly and strongly in an antigen·independent manner. The enhanced chromatin accessibility and gene transcription result in an improved innate immune response after BCG vaccination. Adapted from Chumakov and colleagues.