South Africa: A new phase 2b clinical trial has found thatBacille Calmette–Guérin (BCG) revaccinationdoes not offer protection against sustainedMycobacterium tuberculosis (TB) infectionin adolescents. The study, conducted by Dr. Alexander C. Schmidt and colleagues from the Gates Medical Research Institute, was published in theNew England Journal of Medicineand aimed to assess whether BCG revaccination could reduce the risk of sustained TB infection in a population previously testing negative for TB andHIV. This latest investigation was prompted by earlier findings suggesting that while BCG revaccination may not prevent primary TB infection, it could reduce the risk of persistent infections. To further explore this potential benefit, researchers carried out a double-blind, randomized, placebo-controlled trial involving 1,836 adolescents between the ages of 10 and 18 years in South Africa. Participants were HIV-negative and tested negative on the QuantiFERON-TB Gold (QFT) test at the start of the study. Participants were randomly assigned to receive either the BCG vaccine or a placebo and were monitored over a median follow-up period of 30 months. The primary objective was to assess the rate of sustained QFT test conversion, defined as an initial positive QFT result confirmed by two additional positive results at three and six months. Based on the study, the researchers reported the following findings: The authors concluded that while the vaccine was generally well tolerated and immunogenic, it did not provide measurable protection against sustained M. tuberculosis infection. They noted that the absence of efficacy in preventing infection casts doubt on the likelihood of BCG revaccination offering disease protection. These findings emphasize the continued need for novel TB vaccines that are effective in preventing both infection and disease, particularly in high-risk populations such as adolescents in TB-endemic regions. Schmidt AC, Fairlie L, Hellström E, Luabeya Kany Kany A, Middelkoop K, Naidoo K, Nair G, Gela A, Nemes E, Scriba TJ, Cinar A, Frahm N, Mogg R, Kaufman D, Dunne MW, Hatherill M; BCG REVAX Study Team. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection. N Engl J Med. 2025 May 8;392(18):1789-1800. doi: 10.1056/NEJMoa2412381. PMID: 40334156; PMCID: PMC12061034.