tetano
Editor, Senior Moderator
Respir Res. 2014 May 20;15(1):60. [Epub ahead of print]
Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization.
Rajapaksa A, Ho J, Qi A, Nguyen TH, Tate M, Bischof R, Piedrafita D, McIntosh M, Yeo L, Meeusen E, Coppel R, Friend J.
Abstract
BACKGROUND:
Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the needfor needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route tovaccine production without side effects or reliance on cold chain storage, its delivery to the lung hasproved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliverlarge biomolecules like pDNA intact due to the shear stresses present during nebulization.
METHODS:
In vitro structural analysis followed by in vivo protein expression studies served in assessing theintegrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunizationtrials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutininH1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinationsusing pDNA for influenza was nebulised and delivered via 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-nebulizedpDNA was delivered to a male Swiss mouse via intratracheal instillation. Effective systemic andmucosal antibody responses was found in rats via post-nebulized, condensed fluid instillation. Significantly,we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNAencoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.
PMID:
24884387
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24884387
Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization.
Rajapaksa A, Ho J, Qi A, Nguyen TH, Tate M, Bischof R, Piedrafita D, McIntosh M, Yeo L, Meeusen E, Coppel R, Friend J.
Abstract
BACKGROUND:
Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the needfor needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route tovaccine production without side effects or reliance on cold chain storage, its delivery to the lung hasproved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliverlarge biomolecules like pDNA intact due to the shear stresses present during nebulization.
METHODS:
In vitro structural analysis followed by in vivo protein expression studies served in assessing theintegrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunizationtrials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutininH1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinationsusing pDNA for influenza was nebulised and delivered via 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-nebulizedpDNA was delivered to a male Swiss mouse via intratracheal instillation. Effective systemic andmucosal antibody responses was found in rats via post-nebulized, condensed fluid instillation. Significantly,we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNAencoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.
PMID:
24884387
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24884387