{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:02:18Z","timestamp":1779310938525,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["ECR\/2017\/003016"],"award-info":[{"award-number":["ECR\/2017\/003016"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB), caused by\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>M.tb.<\/jats:italic>\n                    ), affects one-third of humanity. Despite the availability of effective drug regimens, complete eradication of\n                    <jats:italic>M.tb.<\/jats:italic>\n                    remains challenging due to prolonged treatment duration. Additionally, MDR-TB and co-infection with HIV further exacerbate disease severity. The Bacille Calmette\u2013Gu\u00e9rin (BCG) vaccine has shown inconsistent efficacy due to the absence of Th-1 antigens. Hence, there is a critical need for either a novel vaccine candidate or an efficient booster to enhance BCG\u2019s prophylactic efficacy. In this study, in-house prepared\n                    <jats:italic>M.tb.<\/jats:italic>\n                    -infected alveolar macrophage-derived exosomes (Rv-Exo) and ESAT-6-containing exosomes (ESAT-6 Exo) were characterized based on size, purity, and pathogen-associated molecular patterns (PAMPs), and their epitope mapping was also performed. These\n                    <jats:italic>M.tb.<\/jats:italic>\n                    protein-containing exosomes (MPEs) were utilized for immunization, either alone or as a booster to BCG, and evaluated in BALB\/c mice against experimental\n                    <jats:italic>M.tb.<\/jats:italic>\n                    challenge. Our results demonstrate that ESAT-6 Exo and Rv-Exo, either alone or as a BCG booster, enhanced Th-1-biased immune responses by activating CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, increasing memory T-cell populations, and significantly reducing the\n                    <jats:italic>M.tb.<\/jats:italic>\n                    burden in the lungs, spleen, and lymph nodes of infected mice. These findings highlight the potential of MPE as a promising strategy against TB especially in the BCG-vaccinated population.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1742207","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:47:05Z","timestamp":1773384425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mycobacterium tuberculosis antigen-containing exosomes reinforce BCG vaccine efficacy by augmenting long-term protection and memory response against experimental tuberculosis in BALB-C mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Manu","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sher","family":"Afghan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Singh","sequence":"additional","affiliation":[{"name":"National JALMA Institute of Leprosy and Other Mycobacterial Diseases","place":["Agra, Uttar Pradesh, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iqbal","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meetu","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Interdisciplinary Sciences and Technology, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd","family":"Shahid","sequence":"additional","affiliation":[{"name":"College of Pharmacy & School of Graduate and Post Doctoral Studies, Rosalind Franklin University of Medicine and Science","place":["North Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaikh Muhammad","family":"Atif","sequence":"additional","affiliation":[{"name":"Department of Medicine Infectious Diseases, University of Colorado Anschutz Medical","place":["Aurora, CO, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Saima","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vengala Rao","family":"Yenuganti","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, SRM University-AP","place":["Amaravati, Andhra Pradesh, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mairaj Ahmed","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard","place":["New Delhi, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/jcla.25122","article-title":"Mycobacterium tuberculosis: the mechanism of pathogenicity, immune responses, and diagnostic challenges","volume":"38","author":"Mohammadnabi","year":"2024","journal-title":"J Clin Lab Anal"},{"key":"B2","unstructured":"Global tuberculosis report 2025\n          \n          \n          \n          2025"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169539","article-title":"Comparison of TST and IGRA in diagnosis of latent tuberculosis infection in a high TB-Burden setting","volume":"12","author":"Sharma","year":"2017","journal-title":"PLoS One"},{"key":"B4","volume-title":"Bacille Calmette-Gu\u00e9rin (BCG) vaccine for tuberculosis","year":"2025"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-804543-5.00011-7","article-title":"Mycobacterium tuberculosis: clinical and microbiological aspects","volume-title":"The Microbiology of Respiratory System Infections","author":"Ram\u00edrez-Rueda","year":"2016"},{"key":"B6","article-title":"Treatment of tuberculosis","volume-title":"Morbidity and Mortality Weekly Report","author":"Fleming","year":"2003"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017863","article-title":"Multidrug-Resistant tuberculosis and extensively Drug-Resistant tuberculosis","volume":"5","author":"Seung","year":"2015","journal-title":"Cold Spring Harbor Perspect Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2012.04.002","article-title":"Current status of tuberculosis and recombinant bacillus Calmette-Gu\u00e9rin vaccines","volume":"54","author":"Ohara","year":"2012","journal-title":"J Oral Biosci"},{"key":"B9","unstructured":"Global tuberculosis report 2022\n          \n          \n          \n          2022"},{"key":"B10","unstructured":"New TB vaccine research"},{"key":"B11","doi-asserted-by":"publisher","first-page":"73","DOI":"10.4103\/0974-777x.77299","article-title":"Fundamentals of vaccine immunology","volume":"3","author":"Clem","year":"2011","journal-title":"J Global Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12050483","article-title":"Tuberculosis vaccines and T cell immune memory","volume":"12","author":"Li","year":"2024","journal-title":"Vaccines"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526101","article-title":"IL-12 up-regulates T-bet independently of IFN-gamma in human CD4+ T cells","volume":"35","author":"Ylikoski","year":"2005","journal-title":"Eur J Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10020313","article-title":"Functions of ROS in macrophages and antimicrobial immunity","volume":"10","author":"Herb","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04330-5","article-title":"Small extracellular vesicles: the origins, current status, future prospects, and applications","volume":"16","author":"Zhou","year":"2025","journal-title":"Stem Cell Res Ther"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10010145","article-title":"Composition and Clinical Significance of exosomes in tuberculosis: A systematic literature review","volume":"10","author":"Biadglegne","year":"2021","journal-title":"J Clin Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1435426","article-title":"Exosomes: the next frontier in vaccine development and delivery","volume":"15","author":"Tan","year":"2024","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials \u2013 an ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J Extracellular Vesicles"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-021-03143-4","article-title":"Potential application of exosomes in vaccine development and delivery","volume":"39","author":"Huda","year":"2022","journal-title":"Pharm Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022889","article-title":"RD antigen based nanovaccine imparts long term protection by inducing memory response against experimental murine tuberculosis","volume":"6","author":"Ansari","year":"2011","journal-title":"PLoS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1596016","article-title":"Extracellular vesicle measurements with nanoparticle tracking analysis \u2013 An accuracy and repeatability comparison between NanoSight NS300 and ZetaView","volume":"8","author":"Bachurski","year":"2019","journal-title":"J Extracellular Vesicles"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.11.1801","article-title":"Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases","volume":"11","author":"Mitra","year":"1999","journal-title":"Int Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00154","article-title":"Current and novel approaches to vaccine development against tuberculosis","volume":"2","author":"Cayabyab","year":"2012","journal-title":"Front Cell Infection Microbiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3390\/cells12020317","article-title":"A structural view at vaccine development against M. tuberculosis","volume":"12","author":"Romano","year":"2023","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005934","article-title":"Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A","volume":"4","author":"Whelan","year":"2009","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/iai.70.2.672-678.2002","article-title":"Failure of the Mycobacterium bovis BCG vaccine: Some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis","volume":"70","author":"Brandt","year":"2002","journal-title":"Infection Immun"},{"key":"B27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.medj.2021.11.006","article-title":"Protection against tuberculosis by Bacillus Calmette-Gu\u00e9rin (BCG) vaccination: A historical perspective","volume":"3","author":"Setiabudiawan","year":"2021","journal-title":"Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13191","article-title":"Is mapping the BCG vaccine-induced immune responses the key to improving the efficacy against tuberculosis","volume":"288","author":"Kuan","year":"2020","journal-title":"J Internal Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343727","article-title":"Exosomes carrying mycobacterial antigens can protect mice against Mycobacterium tuberculosis infection","volume":"43","author":"Cheng","year":"2013","journal-title":"Eur J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103638","article-title":"Exosomes isolated from mycobacteria-infected mice or cultured macrophages can recruit and activate immune cells in vitro and in vivo","volume":"189","author":"Singh","year":"2012","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0679-8","article-title":"Extracellular vesicle-mediated MHC cross-dressing in immune homeostasis, transplantation, infectious diseases, and cancer","volume":"40","author":"Zeng","year":"2018","journal-title":"Semin Immunopathology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m111.271155","article-title":"Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2","volume":"286","author":"Valapala","year":"2011","journal-title":"J Biol Chem"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00122-20","article-title":"Vaccine-induced th-1-type response protects against invasive group A streptococcus infection in the absence of opsonizing antibodies","volume":"11","author":"Rivera-Hernandez","year":"2020","journal-title":"mBio"},{"key":"B34","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.immuni.2018.01.006","article-title":"Interleukin-10 directly inhibits CD8+ T cell function by enhancing N-glycan branching to decrease antigen sensitivity","volume":"48","author":"Smith","year":"2018","journal-title":"Immunity"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116450","article-title":"Mechanisms of stimulation of interleukin- 1\u03b2 and tumor necrosis factor-\u03b1 by Mycobacterium tuberculosis components","volume":"91","author":"Zhang","year":"1993","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2001-2010.2001","article-title":"Induction of iNOS-NO by lipoarabinomannan of Mycobacterium tuberculosis is mediated by MEK1-ERK, MKK7-JNK, and NF- \u03baB signaling pathways","volume":"69","author":"Chan","year":"2001","journal-title":"Infection Immun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.01.008","article-title":"Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy","volume":"34","author":"Li","year":"2024","journal-title":"Bioactive Materials"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1742207\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:47:13Z","timestamp":1773384433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1742207\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2026.1742207"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1742207","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"article-number":"1742207"}}