TOPLINE:
Bacille Calmette-Guérin (BCG) revaccination showed no efficacy in preventing sustained Mycobacterium tuberculosis infection compared with placebo in adolescents, with similar rates of QuantiFERON-TB (QFT) test conversion from negative to positive.
METHODOLOGY:
- In a previous trial, BCG revaccination did not prevent primary M tuberculosis infection but did reduce the risk for sustained infections, prompting further study in a wider population.
- Researchers conducted a phase 2b, randomized study to evaluate the efficacy of BCG revaccination for the prevention of sustained M tuberculosis infection in South Africa.
- A total of 1836 adolescents (age, 10-18 years), who tested negative for HIV and had negative QFT test results at screening, were randomly assigned to receive either the BCG vaccine or placebo and were followed up for a median of 30 months.
- A sustained M tuberculosis infection was defined as a sustained QFT test conversion from negative to positive (≥ 0.35 IU/mL interferon gamma), occurring any time after the first negative QFT test, followed by positive tests confirmed at 3 and 6 months.
- The primary endpoint was sustained QFT test conversion, and the secondary endpoints were the safety and reactogenicity of BCG revaccination.
TAKEAWAY:
- BCG revaccination showed no protective effect against sustained M tuberculosis infection, with similar QFT test conversion rates in the vaccine and placebo groups (hazard ratio, 1.04; P = .58), with a vaccine efficacy of -3.8% (95% CI, -48.3 to 27.4).
- The frequencies of antigen-specific CD4 T cells expressing various cytokines were higher in the BCG revaccination group than in the placebo group, and they remained higher than those at baseline even 6 months postvaccination.
- Most adverse events were mild to moderate. Serious adverse events occurred in 0.3% of participants in each group and were unrelated to the vaccine or placebo, with no deaths or treatment discontinuations.
IN PRACTICE:
“Although this trial does not allow us to draw firm conclusions on the efficacy of BCG revaccination for the prevention of disease, the lack of vaccine efficacy with respect to prevention of infection probably decreases the likelihood of BCG revaccination conferring protection against disease,” the study authors wrote.
SOURCE:
The study was led by Alexander Schmidt, MD, Gates Medical Research Institute, Cambridge, Massachusetts. It was published online on May 7, 2025, in The New England Journal of Medicine.
LIMITATIONS:
Enrollment was paused for 4 months due to the COVID-19 pandemic, which may have contributed to a lower incidence of QFT test conversions.
DISCLOSURES:
The study was supported by the Gates Foundation. One author reported being an employee of the Gates Medical Research Institute. Some authors reported being employees of pharmaceutical companies such as GSK, Pfizer, and Third Rock Ventures, LLC, and owning stocks in these companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.