{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:21:33Z","timestamp":1782739293141,"version":"3.54.5"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T00:00:00Z","timestamp":1560470400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Foundation for Innovation"},{"name":"Ontario Government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The development of strategies to accelerate disease resolution and shorten antibiotic therapy is imperative in curbing the global tuberculosis epidemic. Therapeutic application of novel vaccines adjunct to antibiotics represents such a strategy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>By using a murine model of pulmonary tuberculosis (TB), we have investigated whether a single respiratory mucosal therapeutic delivery of a novel chimpanzee adenovirus-vectored vaccine expressing Ag85A (AdCh68Ag85A) accelerates TB disease control in conjunction with antibiotics and restricts pulmonary disease rebound after premature (nonsterilizing) antibiotic cessation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We find that immunotherapy via the respiratory mucosal, but not parenteral, route significantly accelerates pulmonary mycobacterial clearance, limits lung pathology, and restricts disease rebound after premature antibiotic cessation. We further show that vaccine-activated antigen-specific T cells, particularly CD8 T cells, in the lung play an important role in immunotherapeutic effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results indicate that a single-dose respiratory mucosal immunotherapy with AdCh68Ag85A adjunct to antibiotic therapy has the potential to significantly accelerate disease control and shorten the duration of conventional treatment. Our study provides the proof of principle to support therapeutic applications of viral-vectored vaccines via the respiratory route.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiz306","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T15:11:28Z","timestamp":1560352288000},"page":"1355-1366","source":"Crossref","is-referenced-by-count":14,"title":["Single-Dose Mucosal Immunotherapy With Chimpanzee Adenovirus-Based Vaccine Accelerates Tuberculosis Disease Control and Limits Its Rebound After Antibiotic Cessation"],"prefix":"10.1093","volume":"220","author":[{"given":"Sam","family":"Afkhami","sequence":"first","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky","family":"Lai","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"D\u2019agostino","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Vaseghi-Shanjani","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zganiacz","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushi","family":"Yao","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mangalakumari","family":"Jeyanathan","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Xing","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. 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