{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:17:24Z","timestamp":1787563044693,"version":"build-2736575974"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide, causing over a million deaths annually. The only licensed TB vaccine for human use, Bacille Calmette-Gu\u00e9rin (BCG), a mycobacteria-based live-attenuated vaccine, confers immunity to children but fails to efficiently protect adults from pulmonary TB. Several TB vaccine candidates have been developed over the last two decades, but some have failed to provide substantially better protection than BCG in clinical trials. Most of these vaccine candidates were initially evaluated for their protective capacity in mouse models of TB. With the availability of several mouse strains, vaccination routes and\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) challenge strains, to-date there is no consensus in the field about the predictive value of different murine models of TB, and it remains a matter of debate whether host genetics or vaccine-driven parameters primarily determine vaccine efficacy. Here we reviewed the performance of all TB vaccine candidates that have entered clinical trials over the last 25 years. We extracted protective efficacy data from all published studies that utilized mouse models to assess vaccination efficacy. The efficacy of each vaccine candidate to reduce lung bacterial burden depending on the mouse genotype, the vaccine administration route, and the\n                    <jats:italic>Mtb<\/jats:italic>\n                    challenge strain at different time-points was evaluated. Our data reveals insights into the effect of experimental parameters on vaccine performance and emphasizes the potential benefits of standardizing TB mouse models across vaccination-challenge studies to identify pre-clinical vaccine candidates with the highest potential to succeed.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1609136","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T01:25:04Z","timestamp":1748481904000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A review of the efficacy of clinical tuberculosis vaccine candidates in mouse models"],"prefix":"10.3389","volume":"16","author":[{"given":"Lidia","family":"del Pozo-Ramos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kupz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"B1","unstructured":"Global Tuberculosis Report -2024\n          \n          \n          \n          2024"},{"key":"B2","unstructured":"Tuberculosis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu625","article-title":"Cough and the transmission of tuberculosis","volume":"211","author":"Turner","year":"2015","journal-title":"J Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix362","article-title":"What We Know about Tuberculosis Transmission: An Overview","volume":"216","author":"Churchyard","year":"2017","journal-title":"J Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136222","article-title":"The knowns and unknowns of latent Mycobacterium tuberculosis infection","volume":"131","author":"Boom","year":"2021","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017601","article-title":"Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: A systematic review","volume":"6","author":"Tiemersma","year":"2011","journal-title":"PloS One"},{"key":"B7","unstructured":"The Sustainable Development Goals Report"},{"key":"B8","unstructured":"Global Tuberculosis Report 2022\n          \n          \n          2022"},{"key":"B9","doi-asserted-by":"publisher","first-page":"5998","DOI":"10.1016\/j.vaccine.2014.07.113","article-title":"Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG)","volume":"32","author":"Copin","year":"2014","journal-title":"Vaccine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MGM2-0028-2013","article-title":"BCG vaccines","volume":"2","author":"Tran","year":"2014","journal-title":"Microbiol Spectr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.medj.2021.11.006","article-title":"Protection against tuberculosis by Bacillus Calmette-Gu\u00e9rin (BCG) vaccination: A historical perspective","volume":"3","author":"Setiabudiawan","year":"2022","journal-title":"Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/vaccines10010057","article-title":"After 100 years of BCG immunization against tuberculosis, what is new and still outstanding for this vaccine","volume":"10","author":"la Torre","year":"2021","journal-title":"Vaccines"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2021.2007711","article-title":"BCG vaccination strategies against tuberculosis: updates and perspectives","volume":"17","author":"Qu","year":"2021","journal-title":"Hum Vaccin Immunother"},{"key":"B14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41586-019-1817-8","article-title":"Prevention of tuberculosis in macaques after intravenous BCG immunization","volume":"577","author":"Darrah","year":"2020","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1080\/14760584.2019.1692657","article-title":"Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges","volume":"18","author":"Stylianou","year":"2019","journal-title":"Expert Rev Vacc"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0307877","DOI":"10.1371\/journal.pone.0307877","volume":"19","author":"Shi","year":"2024","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/S11030-022-10515-4","article-title":"Modeling of MT. 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