{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:05Z","timestamp":1787018345913,"version":"build-2736575974"},"reference-count":90,"publisher":"American Society for Clinical Investigation","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,19]]},"abstract":"\n BACKGROUND<\/jats:title>\n Bacille Calmette-Gu\u00e9rin (BCG) vaccine is protective against Tuberculosis (TB) in children, but its efficacy wanes with age. Consequently, determining if BCG revaccination augments anti-TB immunity in young adults in TB endemic regions is vital.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Two hundred healthy adults, BCG vaccinated at birth, were tested for their IFN-\u03b3 release assay (IGRA) status. Of these, 28 IGRA\n +<\/jats:sup>\n and 30 IGRA\n \u2013<\/jats:sup>\n were BCG revaccinated, and 24 IGRA\n +<\/jats:sup>\n and 23 IGRA\n \u2013<\/jats:sup>\n subjects served as unvaccinated controls. T and innate cell responses to mycobacterial antigens were analyzed by 14-color flow cytometry over 34 weeks.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n IFN-\u03b3 and\/or IL-2 Ag85A- and BCG-specific CD4\n +<\/jats:sup>\n and CD8\n +<\/jats:sup>\n T cell responses were boosted by revacciantion at 4 and 34 weeks, respectively, and were > 2-fold higher in IGRA\n +<\/jats:sup>\n compared with IGRA\n \u2013<\/jats:sup>\n vaccinees. Polyfunctional Ag85A, BCG, and mycobacterium tuberculosis (Mtb) latency Ag\u2013specific (LTAg-specific) CD4\n +<\/jats:sup>\n T cells expressing up to 8 cytokines were also significantly enhanced in both IGRA\n +<\/jats:sup>\n and IGRA\n \u2013<\/jats:sup>\n vaccinees relative to unvaccinated controls, most markedly in IGRA\n +<\/jats:sup>\n vaccinees. A focused analysis of Th17 responses revealed expansion of Ag85A-, BCG-, and LTAg-specific total IL-17A\n +<\/jats:sup>\n ,IL-17F\n +<\/jats:sup>\n ,IL-22\n +<\/jats:sup>\n , and IL-10\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n T cell effectors in both IGRA\n +<\/jats:sup>\n and IGRA\n \u2013<\/jats:sup>\n subjects. Also, innate IFN-\u03b3\n +<\/jats:sup>\n NK\/\u03b3\u03b4\/NKT cell responses were higher in both IGRA\n +<\/jats:sup>\n and IGRA\n \u2013<\/jats:sup>\n vaccinees compared with controls. This is the first evidence to our knowledge that BCG revaccination significantly boosts antimycobacterial Th1\/Th17 responses in IGRA\n +<\/jats:sup>\n and IGRA\n \u2013<\/jats:sup>\n subjects.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n These data show that BCG revaccination is immunogenic in IGRA\n \u2013<\/jats:sup>\n and IGRA\n +<\/jats:sup>\n subjects, implying that Mtb preinfection in IGRA\n +<\/jats:sup>\n subjects does not impact immunogenicity. This has implications for public health and vaccine development strategies.\n <\/jats:p>\n <\/jats:sec>\n \n FUNDING<\/jats:title>\n This work was funded principally by DBT-NIH (BT\/MB\/Indo-US\/HIPC\/2013).<\/jats:p>\n <\/jats:sec>","DOI":"10.1172\/jci.insight.130540","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T12:02:19Z","timestamp":1574164939000},"source":"Crossref","is-referenced-by-count":62,"title":["BCG revaccination boosts adaptive polyfunctional Th1\/Th17 and innate effectors in IGRA+ and IGRA\u2013 Indian adults"],"prefix":"10.1172","volume":"4","author":[{"given":"Srabanti","family":"Rakshit","sequence":"first","affiliation":[{"name":"Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-4786","authenticated-orcid":true,"given":"Vasista","family":"Adiga","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-3106","authenticated-orcid":true,"given":"Bharath K.","family":"Sundararaj","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravat Nalini","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology of HIV-TB Co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kenneth","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and"},{"name":"Department of Pulmonary Medicine, St. John\u2019s Research Institute, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and"},{"name":"Department of Pulmonary Medicine, St. John\u2019s Research Institute, Bangalore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Bonam","sequence":"additional","affiliation":[{"name":"Arogyavaram Medical Centre, Madanapalle, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Johnson","sequence":"additional","affiliation":[{"name":"Arogyavaram Medical Centre, Madanapalle, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees L.M.C.","family":"Franken","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3706-3403","authenticated-orcid":true,"given":"Tom H.M.","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-9090","authenticated-orcid":true,"given":"Greg","family":"Finak","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-0232","authenticated-orcid":true,"given":"Raphael","family":"Gottardo","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth D.","family":"Stuart","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-4618","authenticated-orcid":true,"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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