Electroporation for DNA immunization: clinical application

Abstract

DNA immunization is an attractive technology owing to its potential to induce balanced and long-lived immune responses. However, progress into the clinic has been hampered by the relatively low magnitude of the immune response typically induced following administration in large target species, which is likely due to low transfection efficiency as well as insufficient recruitment of antigen-presenting cells to the injection site. Electroporation addresses both of these limitations by inducing transiently enhanced cell membrane permeability, thus facilitating uptake of the DNA into the host cell and creating a low level of inflammation conducive to enhanced influx of antigen-presenting cells to the injection site. Consequently, electroporation-mediated delivery of DNA vaccines results in very significant improvements in the transfection efficiency and immune responses in comparison to conventional injection. Importantly, electroporation is effective in virtually every animal model tested to date and has a favorable safety profile, which is promising for clinical application. In support of the potential for electroporation in human disease situations, early clinical results suggest that the immunogenicity of DNA vaccines is greatly improved when delivered with electroporation.

Keywords::

• clinical applications
• DNA vaccine
• electroporation

Acknowledgements

The authors would like to thank all current and previous members of the laboratory, colleagues and the animal care group at VIDO/Intervac, University of Saskatchewan and Ichor Medical Systems, Inc. who contributed to this work.

Financial & competing interests disclosure

Work in Sylvia van Drunen Littel-van den Hurk’s laboratory is supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Krembil Foundation, Saskatchewan Agriculture, Food and Rural Revitalization, Alberta Livestock Industry Development Fund, Alberta Beef Producers, Agriculture and Food Council of Alberta, and Beef Cattle Industry Development Fund (British Columbia). Sylvia van Drunen Littel-van den Hurk is employed by the University of Saskatchewan, and D Hannaman is an employee and minority shareholders in Ichor Medical Systems, Inc. Ichor Medical Systems, Inc. is a minority owner of Cyto Pulse Sciences, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.