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Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization

BACKGROUND: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the l...

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Autores principales: Rajapaksa, Anushi E, Ho, Jenny J, Qi, Aisha, Bischof, Rob, Nguyen, Tri-Hung, Tate, Michelle, Piedrafita, David, McIntosh, Michelle P, Yeo, Leslie Y, Meeusen, Els, Coppel, Ross L, Friend, James R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040411/
https://www.ncbi.nlm.nih.gov/pubmed/24884387
http://dx.doi.org/10.1186/1465-9921-15-60
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author Rajapaksa, Anushi E
Ho, Jenny J
Qi, Aisha
Bischof, Rob
Nguyen, Tri-Hung
Tate, Michelle
Piedrafita, David
McIntosh, Michelle P
Yeo, Leslie Y
Meeusen, Els
Coppel, Ross L
Friend, James R
author_facet Rajapaksa, Anushi E
Ho, Jenny J
Qi, Aisha
Bischof, Rob
Nguyen, Tri-Hung
Tate, Michelle
Piedrafita, David
McIntosh, Michelle P
Yeo, Leslie Y
Meeusen, Els
Coppel, Ross L
Friend, James R
author_sort Rajapaksa, Anushi E
collection PubMed
description BACKGROUND: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization. METHODS: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep. RESULTS: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation. CONCLUSION: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways.
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spelling pubmed-40404112014-06-03 Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization Rajapaksa, Anushi E Ho, Jenny J Qi, Aisha Bischof, Rob Nguyen, Tri-Hung Tate, Michelle Piedrafita, David McIntosh, Michelle P Yeo, Leslie Y Meeusen, Els Coppel, Ross L Friend, James R Respir Res Research BACKGROUND: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization. METHODS: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep. RESULTS: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation. CONCLUSION: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways. BioMed Central 2014 2014-05-20 /pmc/articles/PMC4040411/ /pubmed/24884387 http://dx.doi.org/10.1186/1465-9921-15-60 Text en Copyright © 2014 Rajapaksa et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rajapaksa, Anushi E
Ho, Jenny J
Qi, Aisha
Bischof, Rob
Nguyen, Tri-Hung
Tate, Michelle
Piedrafita, David
McIntosh, Michelle P
Yeo, Leslie Y
Meeusen, Els
Coppel, Ross L
Friend, James R
Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title_full Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title_fullStr Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title_full_unstemmed Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title_short Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
title_sort effective pulmonary delivery of an aerosolized plasmid dna vaccine via surface acoustic wave nebulization
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040411/
https://www.ncbi.nlm.nih.gov/pubmed/24884387
http://dx.doi.org/10.1186/1465-9921-15-60
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