53 Arbues A, Aguilo JI, Gonzalo-Asensio J, et al. Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. Vaccine 2013 31: 4867–4873. 54 Martin C, Marinova D, Aguilo N, et al. MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG. Vaccine 2021 39: 7277–7285. 55 Mangtani P, Abubakar I, Ariti C, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis 2014 58: 470–480. 56 Karonga Prevention Trial Group. Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Lancet 1996 348: 17–24. 57 Rodrigues LC, Pereira SM, Cunha SS, et al. Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial. Lancet 2005 366: 1290–1295. 58 Roy A, Eisenhut M, Harris RJ, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ 2014 349: g4643. 59 Barreto ML, Pereira SM, Pilger D, et al. Evidence of an effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: second report of the BCG-REVAC cluster-randomised trial. Vaccine 2011 29: 4875–4877. 60 Glynn JR, Fielding K, Mzembe T, et al. BCG re-vaccination in Malawi: 30-year follow-up of a large, randomised, double-blind, placebo-controlled trial. Lancet Glob Health 2021 9: e1451–e1459. 61 Larsen SE, Williams BD, Rais M, et al. It takes a village: the multifaceted immune response to Mycobacterium tuberculosis infection and vaccine-induced immunity. Front Immunol 2022 13: 840225. 62 Morgan J, Muskat K, Tippalagama R, et al. Classical CD4 T cells as the cornerstone of antimycobacterial immunity. Immunol Rev 2021 301: 10–29. 63 Tameris MD, Hatherill M, Landry BS, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 2013 381: 1021–1028. 64 Kagina BM, Abel B, Scriba TJ, et al. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette–Guerin vaccination of newborns. Am J Respir Crit Care Med 2010 182: 1073–1079. 65 Fletcher HA, Filali-Mouhim A, Nemes E, et al. Human newborn bacille Calmette–Guerin vaccination and risk of tuberculosis disease: a case–control study. BMC Med 2016 14: 76. 66 Fletcher HA, Snowden MA, Landry B, et al. T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nat Commun 2016 7: 11290. 67 Flynn JL, Chan J. Immune cell interactions in tuberculosis. Cell 2022 185: 4682–4702. 68 Khader SA, Divangahi M, Hanekom W, et al. Targeting innate immunity for tuberculosis vaccination. J Clin Invest 2019 129: 3482–3491. 69 Darrah PA, Zeppa JJ, Wang C, et al. Airway T cells are a correlate of i.v. Bacille Calmette–Guerin-mediated protection against tuberculosis in rhesus macaques. Cell Host Microbe 2023 31: 962–977.e8. 70 Plotkin SA, Gilbert PB. Nomenclature for immune correlates of protection after vaccination. Clin Infect Dis 2012 54: 1615–1617. 71 WHO. Correlates of Vaccine-induced Protection: Methods and Implications. Geneva, WHO, 2013. 72 Nemes E, Fiore-Gartland A, Boggiano C, et al. The quest for vaccine-induced immune correlates of protection against tuberculosis. Vaccine Insights 2022 1: 165–181. 73 WHO. An Investment Case for New Tuberculosis Vaccines. Geneva, WHO, 2022. 74 WHO. WHO Evidence Considerations for Vaccine Policy Development. Geneva, WHO, 2022. 75 Houben RM, Dodd PJ. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 2016 13: e1002152. 76 Abubakar I, Drobniewski F, Southern J, et al. Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study. Lancet Infect Dis 2018 18: 1077–1087. 77 Harris RC, Sumner T, Knight GM, et al. Potential impact of tuberculosis vaccines in China, South Africa, and India. Sci Transl Med 2020 12: eaax4607. 78 Moyo S, Ismail F, van der Walt M, et al. Prevalence of bacteriologically confirmed pulmonary tuberculosis in South Africa, 2017–19: a multistage, cluster-based, cross-sectional survey. Lancet Infect Dis 2022 22: 1172–1180. Disclosures: E. Nemes reports receiving the following, outside the submitted work: grants or contracts from the US National Institutes of Health, the Bill &Melinda Gates Foundation, the Gates Medical Research Institute, and the European and Developing Countries Clinical Trials Partnership payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events for Seattle Children’s Hospital and support for attending meetings and/or travel from the Bill &Melinda Gates Foundation. E. Nemes reports the following 176 https://doi.org/10.1183/2312508X.10024922 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY