{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T02:47:01Z","timestamp":1776048421987,"version":"3.50.1"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"DHAC | National Health and Medical Research Council","award":["GNT1191368"],"award-info":[{"award-number":["GNT1191368"]}]},{"DOI":"10.13039\/501100000925","name":"DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1194325"],"award-info":[{"award-number":["GNT1194325"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              A\n              <jats:italic>Mycobacterium ulcerans<\/jats:italic>\n              human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate\n              <jats:italic>M. ulcerans<\/jats:italic>\n              JKD8049 in na\u00efve and\n              <jats:italic>Mycobacterium bovis<\/jats:italic>\n              bacille Calmette\u2013Gu\u00e9rin (BCG)-vaccinated BALB\/c mice. All 10 na\u00efve mice were successfully infected with 20 colony-forming units (CFU) of\n              <jats:italic>M. ulcerans<\/jats:italic>\n              [95% confidence interval (CI) 17\u201322 CFU] with a mean time to visible lesion of 86 days (95% CI 79\u201392 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the na\u00efve controls of 24 days (\n              <jats:italic>P<\/jats:italic>\n              = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this\n              <jats:italic>in vivo<\/jats:italic>\n              model and highlights both the promise and the problems with trying to induce protective immunity against\n              <jats:italic>M. ulcerans<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB\/c mice using a carefully characterized, low-dose inoculum of\n              <jats:italic>Mycobacterium ulcerans<\/jats:italic>\n              JKD8049 (our proposed CHIM strain). We also demonstrate that\n              <jats:italic>Mycobacterium bovis<\/jats:italic>\n              bacille Calmette\u2013Gu\u00e9rin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00555-24","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:01:32Z","timestamp":1719320492000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["A\n            <i>Mycobacterium ulcerans<\/i>\n            vaccine pilot trial using an accurate low-dose challenge"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-8199","authenticated-orcid":true,"given":"Stephen","family":"Muhi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-123X","authenticated-orcid":true,"given":"Timothy P.","family":"Stinear","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"WHO Collaborating Centre for Mycobacterium ulcerans, Victorian Infectious Disease Reference Laboratory (VIDRL), Doherty Institute, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2512.190427"},{"key":"e_1_3_4_3_2","unstructured":"Locally transmitted Buruli ulcer cases identified on the NSW south coast. 2023. Available from: https:\/\/www.snswlhd.health.nsw.gov.au\/about-us\/newsroom\/media-releases\/locally-transmitted-buruli-ulcer-cases-identified. Retrieved 28 Feb 2024."},{"key":"e_1_3_4_4_2","unstructured":"Health advisory: Buruli ulcer is spreading. 2023. Available from: https:\/\/www.health.vic.gov.au\/health-advisories\/buruli-ulcer-is-spreading. Retrieved 28 Feb 2024."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011394"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.05.092"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005553"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01553-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01791.x"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200700411"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.2.774-783.2003"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.5694\/mja2.52096"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","unstructured":"Muhi S Buultjens AH Porter JL Marshall JL Doerflinger M Pidot SJ O\u2019Brien DP Johnson PDR Lavender CJ Globan M McCarthy J Osowicki J Stinear TP. 2024. Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model. bioRxiv 18:e0011979. doi:10.1101\/2024.02.08.579445","DOI":"10.1101\/2024.02.08.579445"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01485-09"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000985"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02971-06"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00753-19"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74419"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006323"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00555-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00555-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T13:19:44Z","timestamp":1722950384000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.00555-24"}},"subtitle":[],"editor":[{"given":"Varadharajan","family":"Sundaramurthy","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":18,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8,6]]}},"alternative-id":["10.1128\/spectrum.00555-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.00555-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]},"assertion":[{"value":"2024-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00555-24"}}