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Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis
Open accessAbstract
Vaccines that drive robust T-cell immunity against Mycobacterium tuberculosis (Mtb) are needed both for prophylactic and therapeutic purposes. We have recently developed a synthetic vaccine delivery platform with Pluronic-stabilized polypropylene sulfide nanoparticles (NPs), which target lymphoid tissues by their small size (∼ 30 nm) and which activate the complement cascade by their surface chemistry. Here we conjugated the tuberculosis antigen Ag85B to the NPs (NP-Ag85B) and compared their efficacy in eliciting relevant immune responses in mice after intradermal or pulmonary administration. Pulmonary administration of NP-Ag85B with the adjuvant CpG led to enhanced induction of antigen-specific polyfunctional Th1 responses in the spleen, the lung and lung-draining lymph nodes as compared to soluble Ag85B with CpG and to the intradermally-delivered formulations. Mucosal and systemic Th17 responses were also observed with this adjuvanted NP formulation and vaccination route, especially in the lung. We then evaluated protection induced by the adjuvanted NP formulation following a Mtb aerosol challenge and found that vaccination with NP-Ag85B and CpG via the pulmonary route displayed a substantial reduction of the lung bacterial burden, both compared to soluble Ag85B with CpG and to the corresponding intradermally delivered formulations. These findings highlight the potential of administrating NP-based formulations by the pulmonary route for TB vaccination.
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“Pulmonary administration of the common TB antigen 85B conjugated to poly(propylene sulphide) nanoparticles demonstrated improved protection in mice after they were challenged with aerosolized M. tuberculosis (ref. 135 ).”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [135]
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Metadata
- Authors
- Ballester, M., Nembrini, C., Dhar, N., de Titta, A., de Piano, C., Pasquier, M., Simeoni, E., van der Vlies, A. J., McKinney, J. D., Hubbell, J. A., & Swartz, M. A.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Hubbell, Jeffrey A.
- Swartz, Melody A.
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 29
- Issue
- 40
- Pages
- 6959-6966
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W1967877494
- Cited by
- 130
- References
- 33
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 1 · 2021: 9 · 2020: 6 · 2019: 8 · 2018: 13 · 2017: 9 · 2016: 7 · 2015: 7 · 2014: 15 · 2013: 16 · 2012: 10
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Bill and Melinda Gates Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- tuberculosis vaccination, Ag85B, CpG adjuvant, nanoparticle conjugation, Th1 response, Th17 response, Mycobacterium tuberculosis, aerosol challenge, lung bacterial burden, complement activation
- MeSH terms
- Acyltransferases, Animals, Antigens, Bacterial, Bacterial Proteins, Complement System Proteins, Dendritic Cells, Lung, Lymph Nodes, Mice, Inbred C57BL, Mycobacterium tuberculosis, Particle Size, Polypropylenes, Spleen, Tuberculosis, Vaccines, Synthetic, Th1 Cells, Immunoconjugates, CpG Islands, Tuberculosis Vaccines, Mice, Nanoparticles, Th17 Cells
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