BCG Revaccination for the Prevention of <i>Mycobacterium tuberculosis</i> Infection
Alexander C. Schmidt, Lee Fairlie, Elizabeth Hellström, Angelique Luabeya Kany Kany, Keren Middelkoop, Kogieleum Naidoo, Gonasagrie Nair, Anele Gela, Elisa Nemes, Thomas J. Scriba, Ahu ÇINAR, Nicole Frahm, Robin Mogg, David R. Kaufman, Michael W. Dunne, Mark Hatherill
Abstract
BACKGROUND: release assay) from negative to positive, followed by two additional positive QFT tests at 3 and 6 months after the initial conversion (a secondary end point). A vaccine efficacy of 45% (95% confidence interval [CI], 6 to 68) was observed. METHODS: infection around the time that the vaccine or placebo was administered. Hazard ratios and 95% confidence intervals were estimated from a stratified Cox proportional-hazards model. RESULTS: A total of 1836 participants underwent randomization; 918 received the BCG vaccine, and 917 received placebo. After a median 30 months of follow-up, a sustained QFT test conversion was observed in 62 of 871 participants in the BCG-vaccine group and 59 of 849 participants in the placebo group. The hazard ratio for a sustained QFT test conversion (BCG vaccine vs. placebo) was 1.04 (95% CI, 0.73 to 1.48), for a vaccine efficacy point estimate of -3.8% (95% CI, -48.3 to 27.4). Adverse events occurred more frequently in the BCG-vaccine group than in the placebo group, and most were due to injection-site reactions (pain, redness, swelling, and ulceration). BCG revaccination induced cytokine-positive type 1 helper CD4 T cells. CONCLUSIONS: infection. (Funded by the Gates Foundation; ClinicalTrials.gov number NCT04152161.).