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

Respiratory Research

James R Friend^1,10  Ross L Coppel⁶  Els Meeusen⁸  Leslie Y Yeo¹  Michelle P McIntosh⁹  David Piedrafita⁷  Michelle Tate⁴  Tri-Hung Nguyen⁹  Rob Bischof²  Aisha Qi^1,10  Jenny J Ho³  Anushi E Rajapaksa⁵ 

[1] RMIT University, Micro Nano Research Facility, 124 La Trobe Street, 3000 Melbourne, Australia;Monash University, Department of Physiology, School of Biomedical Sciences, Wellington Road, 3800 Clayton, Australia;Monash University, Department of Chemical Engineering, Wellington Road, 3800 Clayton, Australia;Monash University, Centre for Innate Immunity & Infectious Disease, Monash Institute of Medical Research, 3800 Clayton, Australia;Critical Care and Neuroscience, Murdoch Children’s Research Institute, 3052 Parkville, Australia;Monash University, Faculty of Medicine, Nursing and Health Sciences, Wellington Road, 3800 Clayton, Australia;Monash University, School of Applied Sciences & Engineering, Wellington Road, 3800 Clayton, Australia;Department of Physiology, School of Biomedical Sciences, Wellington Road, 3800 Clayton, Australia;Monash University, Monash Institute of Pharmaceutical Sciences, 3800 Parkville, Australia;Melbourne Centre for Nanofabrication, 151 Wellington Road, 3800 Clayton, Australia

关键词: Nebulization;    Surface acoustic wave;    Gene therapy;   

Others  :  790267
DOI  :  10.1186/1465-9921-15-60

 received in 2014-01-21, accepted in 2014-04-25,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Rajapaksa et al.; licensee BioMed Central Ltd.

【 图 表 】

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