{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:48:52Z","timestamp":1767901732015,"version":"3.49.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1044343"],"award-info":[{"award-number":["APP1044343"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1043225"],"award-info":[{"award-number":["APP1043225"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1153493"],"award-info":[{"award-number":["APP1153493"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Department of Foreign Affairs and Trade"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The current <jats:italic>Mycobacterium bovis<\/jats:italic> BCG vaccine provides inconsistent protection against pulmonary infection with <jats:italic>Mycobacterium tuberculosis<\/jats:italic>. Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> CD4<jats:sup>+<\/jats:sup> T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> infection. Boosting BCG with rIAVs increased the frequency of IFN-\u03b3-secreting specific T cells (p&lt;0.001) and polyfunctional CD4<jats:sup>+<\/jats:sup> T cells (p&lt;0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection <jats:italic>against M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic>-specific memory T cell responses in the lung, but not protection against <jats:italic>M<\/jats:italic>. <jats:italic>tuberculosis<\/jats:italic> infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0259829","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T18:55:28Z","timestamp":1637261728000},"page":"e0259829","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8070-6323","authenticated-orcid":true,"given":"Heni","family":"Muflihah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Fl\u00f3rido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-4005","authenticated-orcid":true,"given":"Leon C. 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