Chapter 12 How close are we to a new, effective tuberculosis vaccine? Recent advances in the field Angelique Kany Kany Luabeya1,2, Michele Tameris1,2, Justin Shenje1,2, Anele Gela1,2, Elisa Nemes 1,2 ,Thomas J. Scriba 1,2 and Mark Hatherill 1,2 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 2 Dept of Pathology, Division of Immunology, University of Cape Town, Cape Town, South Africa. Corresponding author: Mark Hatherill (Mark.Hatherill@uct.ac.za) Cite as: Luabeya AKK, Tameris M, Shenje J, et al. How close are we to a new, effective tuberculosis vaccine? Recent advances in the field. In: García-Basteiro AL, Öner Eyüboğlu F, Rangaka MX, eds. The Challenge of Tuberculosis in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2023 pp. 164–177 [https://doi.org/10.1183/2312508X.10024922]. @ERSpublications The most advanced of 14 candidate TB vaccines are expected to deliver licensure efficacy findings by 2028. Global TB vaccine advocacy and advance planning for country-level introduction will be critical to drive demand, funding, implementation and uptake. https://bit.ly/ERSM101 Copyright ©ERS 2023. Print ISBN: 978-1-84984-169-6. Online ISBN: 978-1-84984-170-2. Print ISSN: 2312-508X. Online ISSN: 2312-5098. Fourteen candidate TB vaccines are in clinical development, including eight in phase 2b–3 trials, although there is a paucity of new candidates advancing from preclinical testing. Live mycobacterial vaccines, including recombinant Mycobacterium bovis BCG and live-attenuated Mycobacterium tuberculosis candidates, are entering prevention of disease efficacy trials in infants and adolescents/ adults. Several candidates are in nontraditional efficacy trials to prevent M. tuberculosis infection, treatment failure or recurrent disease. The most promising protein-subunit vaccine, M72/AS01E, is expected to enter a large, multicountry, licensure trial in adolescents/adults, including PLHIV and those with/without prior M. tuberculosis sensitisation. Findings are expected by 2028. Efforts to discover immune correlates of vaccine-mediated protection are ongoing. Accelerated global TB vaccine advocacy, community sensitisation to reduce vaccine hesitancy, modelling of impact and development of the investment case, evidence considerations for policy and a framework for country-level introduction will be critical to drive demand, release funding and promote uptake of a new, effective TB vaccine. Introduction The world has had access to an old but effective TB vaccine for more than a century. Infant BCG vaccination partially protects against TB, especially the most severe extrapulmonary forms, including disseminated and meningitic disease, and mortality in young children [1]. It is for this reason that universal infant BCG vaccination is policy in 156 countries [2]. BCG efficacy wanes 10–15 years after infant vaccination and does not protect sufficiently against adolescent and adult pulmonary disease that drives Mycobacterium tuberculosis transmission and fuels the epidemic [3, 4]. 164 https://doi.org/10.1183/2312508X.10024922