ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicThe Role of Extracellular Vesicles in Advanced Drug and Vaccine DeliveryView all 8 articles
Mycobacterium tuberculosis antigen containing-exosomes reinforce BCG vaccine efficacy by augmenting long term protection and memory response against experimental tuberculosis in BALB-C mice
Provisionally accepted
Manu Sharma1Sher Afghan2
Amit Singh3
M I Alam2
Meetu Agarwal4Mohd. Shahid5Shaikh Muhammad Atif6Saif Khan1Syed Saima Malik1Vengala Rao Yenuganti7
Mairaj Ahmed Ansari1*- 1Department of Biotechnology, Jamia Hamdard University, New Delhi, India
- 2Department of physiology, HIMSR, Jamia Hamdard, New Delhi, India
- 3ICMR - National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, India
- 4Department of Molecular Medicine, SIST, Jamia Hamdard, New Delhi, India
- 5College of Pharmacy, Rosalind Franklin University of Medicine and Sciences, North Chicago, United States
- 6Department of Medicine, Infectious Diseases, University of Colorado, Denever, Department of Medicine, Infectious Diseases, University of Colorado, Colorado, United States
- 7Department of Biological Sciences, SRM University - AP, Amravati, Andhra Pradesh, India
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Abstract-: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb.), inflicts one third of the humanity. Despite the availability of effective drug regimens, complete eradication of M.tb. remains challenging due to prolong treatment duration. Additionally, MDR-TB and co-infection HIV further exacerbate disease severity. The Bacille Calmette–Guérin (BCG) has shown inconsistent efficacy due to absence of Th-1-antigens. Hence, there is a critical need for either a novel vaccine candidate or an efficient booster to enhance BCG's prophylactic efficacy. In this study, in-house prepared M.tb.-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 M.tb. protein-containing exosomes (MPE) were utilized for immunization, either alone or as a booster to BCG, and evaluated in BALB/c mice against experimental M.tb. challenge. Our results demonstrate the ESAT-6 Exo and Rv-Exo, either alone or as a BCG booster, enhanced Th1-biased immune responses by activating CD4⁺ and CD8⁺ T cells, increasing memory T-cell populations, and significantly reducing the M.tb. burden in the lungs, spleen, and lymph nodes of infected mice. There finding highlights the potential of MPE as a promising strategy against TB specially in BCG vaccinated population.
Keywords: BCG, Exosomes, Long term protection, M.tb., Prophylactic vaccine, T cell memoryresponse, Tuberculosis
Received: 08 Nov 2025; Accepted: 06 Feb 2026.
Copyright: © 2026 Sharma, Afghan, Singh, Alam, Agarwal, Shahid, Atif, Khan, Malik, Yenuganti and Ansari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mairaj Ahmed Ansari
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