BCG tuberculosis vaccine only effective in early childhood

A tuberculosis patient with her daughter at Katutura State Hospital, Windhoek, Namibia: only children are effectively protected from tuberculosis by vaccination with the BCG vaccine.

© Christoph Lange

In the early 20th century, French scientists Albert Calmette and Camille Guérin developed a vaccine from the bovine tuberculosis bacterium Mycobacterium bovis, which was named BCG (Bacillus Calmette-Guérin) after its discoverers. Administered at birth to 100 million children worldwide each year, vaccination with BCG shows high efficacy in early childhood. Until now, however, it remained unclear how long this efficacy lasts in older children and adults—a question that an international research team now addressed in a large-scale systematic study.

The study, published in the journal The Lancet Global Health, reports the results of a comprehensive meta-analysis of vaccine protection in 49,686 people who received BCG vaccination at birth—including 1,309 people (2.6 percent) who developed tuberculosis despite vaccination. However, a comparable percentage of tuberculosis-infected individuals (2.5 percent) was also found in a cohort of 18,866 unvaccinated individuals.

When stratified by age, the study found that BCG vaccination effectively protected children under three years of age against pulmonary tuberculosis and children under five years of age against all forms of tuberculosis. In contrast, however, vaccine protection was no longer sufficient in adolescents and adults, explaining the similar rates of tuberculosis cases in the vaccinated and unvaccinated cohorts.

"The World Health Organisation estimates that over 85 percent of tuberculosis cases occur in adults," explains Prof. Christoph Lange of the Research Center Borstel, head of the Clinical Tuberculosis Centre at DZIF and one of the study's authors. "Only new vaccines that also effectively protect adolescents and adults against tuberculosis can decisively improve prevention of the disease."

Currently, more than ten candidate vaccines against tuberculosis are in clinical trials. According to Prof. Lange, a modification of the BCG vaccine being developed at the Max Planck Institute for Infection Biology in Berlin appears promising.

Another significant finding of the study is that the BCG vaccine—beyond protection against tuberculosis—appears to protect children up to the age of 14 against death from infectious diseases in general. It is hypothesised that the so-called "trained immunity" effect is responsible for this. According to the hypothesis, vaccination in infancy with a live vaccine leads to non-specific, functional reprogramming of innate immune cells and to non-specific protection against other pathogens. Epidemiological studies in high-incidence countries of tuberculosis show a significant tuberculosis-independent reduction in infant mortality in BCG-vaccinated children. It is particularly interesting that this effect can apparently also be transferred from BCG-vaccinated mothers to their infants.

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