Immunization by a bacterial aerosol
Open accessAbstract
By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization. Microstructural properties are adapted to alter dispersive and aerosol properties independently. Dried “nanomicroparticle” vaccines possess two axes of nanoscale dimensions and a third axis of micrometer dimension; the last one permits effective micrometer-like physical dispersion, and the former provides alignment of the principal nanodimension particle axes with the direction of airflow. Particles formed with this combination of nano- and micrometer-scale dimensions possess a greater ability to aerosolize than particles of standard spherical isotropic shape and of similar geometric diameter. Here, we demonstrate effective application of this biomaterial by using the live attenuated tuberculosis vaccine bacille Calmette–Guérin (BCG). Prepared as a spray-dried nanomicroparticle aerosol, BCG vaccine exhibited high-efficiency delivery and peripheral lung targeting capacity from a low-cost and technically simple delivery system. Aerosol delivery of the BCG nanomicroparticle to normal guinea pigs subsequently challenged with virulent Mycobacterium tuberculosis significantly reduced bacterial burden and lung pathology both relative to untreated animals and to control animals immunized with the standard parenteral BCG.
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In guinea pigs, an aerosolized formulation of BCG nanomicroparticles generated better immune protection and enhanced resistance to TB infection than the standard parenteral BCG formulation.
“When guinea pigs were administered an aerosolized formulation of BCG nanomicroparticles, they generated better immune protection and enhanced resistance to TB infection than when they were immunized with the standard parenteral BCG formulation 134 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [134]
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Large Porous Particles for Pulmonary Drug Delivery
Edwards, D. A., Hanes, J. S., Caponetti, G., Hrkach, J. S., Ben-Jebria, A., Eskew, M. L., Mintzes, J. D., Deaver, D. R., Lotan, N., & Langer, R. (1997) · Science · doi:10.1126/science.276.5320.1868 · Cited by 1,176 · see citing works
Self-citationImmunology of tuberculosis and implications in vaccine development
Flynn, J. L. (2003) · Tuberculosis · doi:10.1016/j.tube.2003.08.010 · Cited by 304 · see citing works
Crowder, T. M., Rosati, J. A., Schroeter, J. D., et al. (2002) · Pharmaceutical Research · doi:10.1023/a:1014426530935 · Cited by 248 · see citing works
Dry Powder Aerosols I: A New Powder Inhalation Device
Bell, J., Hartley, P. S., & Cox, J. S. G. (1971) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600601028 · Cited by 202 · see citing works
Davies, C. (1979) · Journal of Aerosol Science · doi:10.1016/0021-8502(79)90006-5 · Cited by 170 · see citing works
Lu, D., & Hickey, A. J. (2007) · Expert Review of Vaccines · doi:10.1586/14760584.6.2.213 · Cited by 144 · see citing works
Self-citationDrying a tuberculosis vaccine without freezing
Wong, Y.-L., Sampson, S. L., Germishuizen, W. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611430104 · Cited by 92 · see citing works
Self-citationPulmonary DNA vaccination: Concepts, possibilities and perspectives
Bivas‐Benita, M., Ottenhoff, T. H. M., Junginger, H. E., & Borchard, G. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.05.028 · Cited by 70 · see citing works
BCG-induced protection in guinea pigs vaccinated and challenged via the respiratory route
Lagranderie, M., Ravisse, P., Marchal, G., et al. (1993) · Tubercle and Lung Disease · doi:10.1016/0962-8479(93)90067-8 · Cited by 67 · see citing works
Descriptors of irregular particle morphology and powder properties
Hickey, A. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(97)00508-5 · Cited by 66 · see citing works
Self-citationAerodynamic properties of elongated particles of cromoglycic acid
Chan, H., & Gonda, I. (1989) · Journal of Aerosol Science · doi:10.1016/0021-8502(89)90041-4 · Cited by 61 · see citing works
Aerogenic BCG Vaccination Against Tuberculosis in Animal and Human Subjects
Rosenthal, S. R., McEnery, J. T., & Raisys, N. (1968) · Journal of Asthma Research · doi:10.3109/02770906809100348 · Cited by 60 · see citing works
Fults, K., Miller, I. F., & Hickey, A. J. (1997) · Pharmaceutical Development and Technology · doi:10.3109/10837459709022610 · Cited by 55 · see citing works
Self-citationOn the Calculation of Aerodynamic Diameters of Fibers
Gonda, I., & Khalik, A. F. A. E. (1985) · Aerosol Science and Technology · doi:10.1080/02786828508959051 · Cited by 51 · see citing works
The influence of fibre shape in lung deposition-mathematical estimates.
Harris, R. L., & Timbrell, V. (1975) · PubMed · Cited by 30 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [3]Fuchs NA. Mechanics of Aerosols. Oxford, UK: Pergamon; 1964. Size and shape of aerosol particles, pp. 1–20. [Google Scholar]
- [5]Hickey AJ, Fults KA, Pillai RS. Use of particle morphology to influence delivery of drugs from dry powder aerosols. J Biopharm Sci. 1992;3:107–113. [Google Scholar]
- [9]Kottrappa P. In: Rochester Third International Conference on Environmental Toxicity. Mercer TT, Morrow PE, Stober W, editors. Vol 14. Springfield, IL: CC Thomas; 1970. pp. 249–289. [Google Scholar]
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Nanotechnology approaches for global infectious diseases
Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00866-8 · Cited by 520 · see citing works
The status of tuberculosis vaccine development
Schrager, L. K., Vekemens, J., Drager, N., Lewinsohn, D. M., & Olesen, O. F. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(19)30625-5 · Cited by 196 · see citing works
- Authors
- Garcia-Contreras, L., Wong, Y.-L., Muttil, P., Padilla, D., Sadoff, J., DeRousse, J., Germishuizen, W. A., Goonesekera, S., Elbert, K., Bloom, B. R., Miller, R., Fourie, P. B., Hickey, A., & Edwards, D.
- Affiliations
- *University of North Carolina, Chapel Hill, NC 27599-7360;
- Harvard University (US)
- University of North Carolina at Chapel Hill (US)
- Aeras (US)
- Medicine in Need South Africa, Medical Research Council Building Number 1, Soutpansberg Road, Pretoria 0002, South Africa;
- **Manta, 264 Third Street, Cambridge, MA 02142
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-25
- Volume
- 105
- Issue
- 12
- Pages
- 4656-4660
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2290758
- OpenAlex
- W2157675557
- Cited by
- 145
- References
- 15
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 6 · 2020: 9 · 2019: 14 · 2018: 8 · 2017: 8 · 2016: 12 · 2015: 9 · 2014: 8 · 2013: 9 · 2012: 12
- FWCI
- 9.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Bill and Melinda Gates Foundation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- BCG vaccine, tuberculosis, Mycobacterium tuberculosis, spray drying, lung targeting, guinea pig model
- MeSH terms
- Aerosols, Animals, Bacterial Vaccines, BCG Vaccine, Drug Administration Routes, Guinea Pigs, Humidity, Hypersensitivity, Delayed, Immunization, Leucine, Lung, Male, Spleen, Tuberculin, Mycobacterium smegmatis, Microbial Viability
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