{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T13:29:50Z","timestamp":1771680590074,"version":"3.50.1"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1197117"],"award-info":[{"award-number":["GNT1197117"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["Early Postdoc Mobility grant number P2GEP3_178155"],"award-info":[{"award-number":["Early Postdoc Mobility grant number P2GEP3_178155"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1197117"],"award-info":[{"award-number":["GNT1197117"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["Early Postdoc Mobility grant number P2GEP3_178155"],"award-info":[{"award-number":["Early Postdoc Mobility grant number P2GEP3_178155"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Scar formation following bacillus Calmette-Gu\u00e9rin (BCG) vaccination has been associated with lower all-cause mortality; the relation between scar and mycobacteria-specific protection against tuberculosis is debated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the association between BCG skin reaction and mycobacteria-specific immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A post hoc analysis was done among 214 infants in Australia randomized to vaccination with one of three BCG vaccine strains (BCG-Denmark, BCG-Japan, or BCG-Russia) given at birth or BCG-Denmark given at 2 months of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>BCG skin reaction size and characteristics 10 weeks after vaccination were related to the in vitro mycobacteria-specific immune responses measured in stimulated whole blood. The size and characteristics of the skin reaction correlated positively with in vitro immune responses, even after adjusting for BCG vaccine strain and age at vaccination. Specifically, the reaction size and characteristics correlated with the proportion of mycobacteria-specific polyfunctional CD4+ T cells after stimulation with BCG and PPD and, to a lesser extent, after stimulation with Mycobacterium tuberculosis or Mycobacterium ulcerans. A similar correlation was observed with concentrations of IFN-\u03b3, IL-2, tumor necrosis factor, and IL-13 in the supernatant after stimulation with BCG, PPD, and M. tuberculosis and to some degree for the proportions of mycobacteria-specific polyfunctional CD8+ T cells and CD107+ cytotoxic cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BCG skin reaction correlated with the magnitude of mycobacteria-specific T-cell responses. As T-cell responses play a key role in defense against mycobacteria, the relationship between BCG scar formation and protection against tuberculosis should be revisited. This may also extend to the need for BCG revaccination in scar-negative individuals.Clinical trial registered with www.australianclinicaltrials.gov.au\/clinical-trial-registries (ACTRN12608000227392).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202108-1892oc","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T16:33:31Z","timestamp":1641832411000},"page":"830-841","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":12,"title":["Bacillus Calmette-Gu\u00e9rin Skin Reaction Predicts Enhanced Mycobacteria-Specific T-Cell Responses in Infants: A\n                    <i>Post Hoc<\/i>\n                    Analysis of a Randomized Controlled Trial"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-4574","authenticated-orcid":false,"given":"Laure F.","family":"Pittet","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit, the Royal Children\u2019s Hospital Melbourne, Parkville, Victoria, Australia"},{"name":"Infectious Diseases Group and"},{"name":"Department of Paediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-5276","authenticated-orcid":false,"given":"Nora","family":"Fritschi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit and Migrant Health Service, and"},{"name":"Mycobacterial and Migrant Health Research Group, Department of Clinical Research, Children\u2019s University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4007-0807","authenticated-orcid":false,"given":"Marc","family":"Tebruegge","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and"},{"name":"Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"},{"name":"Department of Paediatric Infectious Diseases and Immunology, Evelina London Children\u2019s Hospital, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6480-1374","authenticated-orcid":false,"given":"Binita","family":"Dutta","sequence":"additional","affiliation":[{"name":"Hyloris Pharmaceuticals SA, Li\u00e8ge, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2489-3977","authenticated-orcid":false,"given":"Susan","family":"Donath","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and"},{"name":"Clinical Epidemiology and Biostatistics Unit, Murdoch Children\u2019s Research Institute, Parkville, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8404-4462","authenticated-orcid":false,"given":"Nicole L.","family":"Messina","sequence":"additional","affiliation":[{"name":"Infectious Diseases Group and"},{"name":"Department of Paediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Casalaz","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Mercy Hospital for Women, Heidelberg, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-6154","authenticated-orcid":false,"given":"Willem A.","family":"Hanekom","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, Durban, South Africa; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-9646","authenticated-orcid":false,"given":"Warwick J.","family":"Britton","sequence":"additional","affiliation":[{"name":"Centenary Institute, University of Sydney, Sydney, New South Wales, 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