{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:06:14Z","timestamp":1784124374104,"version":"3.55.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI155345"],"award-info":[{"award-number":["R01 AI155345"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K01 OD033539"],"award-info":[{"award-number":["K01 OD033539"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette\u2013Gu\u00e9rin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8\u03b1\u03b2+ T cells expressing multiple cytokines, and CD8\u03b1\u03b2+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (&amp;gt;105 copies\/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.2400417","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T13:28:00Z","timestamp":1727098080000},"page":"1358-1370","source":"Crossref","is-referenced-by-count":7,"title":["Intravenous Bacillus Calmette\u2013Gu\u00e9rin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus\u2013infected Macaques"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-5727","authenticated-orcid":false,"given":"Solomon","family":"Jauro","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"},{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-9369","authenticated-orcid":false,"given":"Erica C","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"},{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle L","family":"Gleim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon M","family":"Wahlberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9800-3362","authenticated-orcid":false,"given":"Mark A","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8811-8897","authenticated-orcid":false,"given":"Julia C","family":"Chehab","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9147-8573","authenticated-orcid":false,"given":"Alondra E","family":"Lopez-Velazques","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico at Humacao , Humacao ,","place":["Puerto Rico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassaundra L","family":"Ameel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime A","family":"Tomko","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Sakal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"DeMarco","sequence":"additional","affiliation":[{"name":"Human Vaccine Institute, Duke University School of Medicine , Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Jacob","family":"Borish","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5188-8420","authenticated-orcid":false,"given":"Pauline","family":"Maiello","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Lake","family":"Potter","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5169-3714","authenticated-orcid":false,"given":"Philana","family":"Ling Lin","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA"},{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-8981","authenticated-orcid":false,"given":"JoAnne L","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"},{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-5603","authenticated-orcid":false,"given":"Charles A","family":"Scanga","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA"},{"name":"Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"2025020609281187100_r1","volume-title":"Global Tuberculosis Report 2022.","author":"World Health Organization","year":"2022"},{"key":"2025020609281187100_r2","volume-title":"Global Tuberculosis Report 2021.","author":"World Health 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Opin. HIV AIDS"},{"key":"2025020609281187100_r5","doi-asserted-by":"crossref","first-page":"e01728-18","DOI":"10.1128\/JVI.01728-18","article-title":"HIV infection functionally impairs Mycobacterium tuberculosis-specific CD4 and CD8 T-cell responses","volume":"93","author":"Amelio","year":"2019","journal-title":"J. Virol."},{"key":"2025020609281187100_r6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1146\/annurev-immunol-042617-053420","article-title":"The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons","volume":"36","author":"Esmail","year":"2018","journal-title":"Ann. Rev. Immunol."},{"key":"2025020609281187100_r7","doi-asserted-by":"crossref","first-page":"e20200887","DOI":"10.1084\/jem.20200887","article-title":"Type I interferon signaling mediates Mycobacterium tuberculosis\u2013induced macrophage death","volume":"218","author":"Zhang","year":"2021","journal-title":"J. Exp. Med."},{"key":"2025020609281187100_r8","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nature13554","article-title":"Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression","volume":"511","author":"Sandler","year":"2014","journal-title":"Nature"},{"key":"2025020609281187100_r9","first-page":"2879","article-title":"Effects of Th17\/Treg cell imbalance on HIV replication in patients with AIDS complicated with tuberculosis","volume":"15","author":"Li","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"2025020609281187100_r10","doi-asserted-by":"crossref","first-page":"e105594","DOI":"10.15252\/embj.2020105594","article-title":"HIV-1 infection of CD4 T cells impairs antigen-specific B cell function","volume":"39","author":"Kaw","year":"2020","journal-title":"EMBO J."},{"key":"2025020609281187100_r11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4049\/jimmunol.2100073","article-title":"Pre-existing simian immunodeficiency virus infection increases expression of t cell markers associated with activation during early Mycobacterium tuberculosis coinfection and impairs TNF responses in granulomas","volume":"207","author":"Larson","year":"2021","journal-title":"J. Immunol."},{"key":"2025020609281187100_r12","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.3390\/jcm9113575","article-title":"Pathogenesis of human immunodeficiency virus-Mycobacterium tuberculosis co-infection","volume":"9","author":"Wong","year":"2020","journal-title":"J. Clin. 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Microbiol."},{"key":"2025020609281187100_r20","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.chom.2023.05.006","article-title":"Airway T cells are a correlate of i.v. bacille Calmette-Guerin-mediated protection against tuberculosis in rhesus macaques","volume":"31","author":"Darrah","year":"2023","journal-title":"Cell Host Microbe"},{"key":"2025020609281187100_r21","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1038\/s41590-021-01066-1","article-title":"Robust IgM responses following intravenous vaccination with bacille Calmette-Gu\u00e9rin associate with prevention of Mycobacterium tuberculosis infection in macaques","volume":"22","author":"Irvine","year":"2021","journal-title":"Nat. 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Spectr."},{"key":"2025020609281187100_r27","doi-asserted-by":"crossref","first-page":"e00565-18","DOI":"10.1128\/IAI.00565-18","article-title":"Preexisting simian immunodeficiency virus infection increases susceptibility to tuberculosis in Mauritian cynomolgus macaques","volume":"86","author":"Rodgers","year":"2018","journal-title":"Infect. 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