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A challenge in developing an improved TB vaccine has been the lack of understanding what is needed to generate sterilizing immunity against <ns4:italic>Mycobacterium tuberculosis<\/ns4:italic> (Mtb) infection. Several epidemiological observations support the hypothesis that humans can eradicate Mtb following exposure. This has been termed early clearance and is defined as elimination of Mtb infection prior to the development of an adaptive immune response, as measured by a tuberculin skin test or interferon-gamma release assay. Here, we examine research into the likelihood of and possible mechanisms responsible for early clearance in household contacts of patients with active TB. We explore both innate and adaptive immune responses in the lung. Enhanced understanding of these mechanisms could be harnessed for the development of a preventative vaccine or immunotherapy.<\/ns4:p>","DOI":"10.12688\/f1000research.13224.1","type":"journal-article","created":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T07:30:14Z","timestamp":1527233414000},"page":"664","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Early clearance versus control: what is the meaning of a negative tuberculin skin test or interferon-gamma release assay following exposure to Mycobacterium tuberculosis?"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9709-7624","authenticated-orcid":false,"given":"Erin W.","family":"Meermeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-9494","authenticated-orcid":false,"given":"David M.","family":"Lewinsohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,5,25]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"271-86","DOI":"10.1146\/annurev-publhealth-031912-114431","article-title":"Prospects for tuberculosis elimination.","volume":"34","author":"C Dye","year":"2013","journal-title":"Annu Rev Public Health."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"13980-5","DOI":"10.1073\/pnas.0901720106","article-title":"Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics.","volume":"106","author":"L Abu-Raddad","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"475-527","DOI":"10.1146\/annurev-immunol-032712-095939","article-title":"The immune response in tuberculosis.","volume":"31","author":"A O'Garra","year":"2013","journal-title":"Annu Rev Immunol."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"3-20","DOI":"10.1128\/CMR.00034-13","article-title":"Gamma interferon release assays for detection of Mycobacterium tuberculosis infection.","volume":"27","author":"M Pai","year":"2014","journal-title":"Clin Microbiol Rev."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"1176-84","DOI":"10.1164\/rccm.201502-0232OC","article-title":"Risk Assessment of Tuberculosis in Contacts by IFN-\u03b3 Release Assays. 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The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}