ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicHow close are we to understanding immune evasion and development of vaccines for mycobacterial pathogens?View all articles
Intranasal BCG vaccination induces systemic and pulmonary mucosal immune responses against tuberculosis in a goat model
Provisionally accepted
Patricia Cuenca Lara1,2
Miriam Blay-Benach1,2Zoraida Cervera1,2Julia Moraleda1,2
Iker A. Sevilla3
Joseba M Garrido3
Mahavir Prof. Dr. Singh4Sergio López-Soria1,2
Enric Vidal1,2
Mariano Domingo2,5
Bernat Pérez de Val1,2*- 1IRTA-CReSA, Centre for Research on Animal Health, Bellaterra, Spain
- 2Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Bellaterra, Spain
- 3NEIKER Nekazaritza Ikerketa eta Garapenerako Euskal Erakundea SA Derioko Zentroa, Derio, Spain
- 4Lionex Diagnostics and Therapeutics GmbH, Braunschweig, Germany
- 5Universitat Autonoma de Barcelona Departament de Sanitat i d'Anatomia Animals, Bellaterra, Spain
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Early immune containment of mycobacteria at the infection site is key to tuberculosis (TB) vaccine development. Intranasal delivery strategies offer a promising alternative to parenteral BCG vaccination, particularly for pulmonary TB, the predominant clinical form in humans and livestock. This study evaluated the immunogenicity of intranasal BCG and heat-inactivated M. bovis (HIMB) with or without adjuvant, as well as prime-boost strategies combining parenteral BCG or HIMB followed by intranasal HIMB in young goats. Intranasal BCG elicited systemic antigen-specific IFNγ production, with enhanced expansion of CD4⁺IFNγ⁺ and CD8⁺IFNγ⁺ T-cells, comparable to prime-boost regimens. Intranasal BCG and prime-boosted groups also induced higher local proinflammatory responses at the lung mucosa, including proinflammatory cytokine production, expansion of antigen-specific T-cells, and polarization of alveolar macrophages toward activated proinflammatory phenotype. The results underscore the potential of respiratory mucosal BCG delivery to enhance early immune responses against TB infection and support further investigation into its protective efficacy.
Keywords: alveolar macrophages, animal model, BCG, Goat, Heat-inactivatedMycobacterium bovis, mucosal immunity, mucosal vaccines, Tuberculosis
Received: 05 Nov 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Cuenca Lara, Blay-Benach, Cervera, Moraleda, Sevilla, Garrido, Prof. Dr. Singh, López-Soria, Vidal, Domingo and Pérez de Val. 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: Bernat Pérez de Val
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