Genetic Immunization with Plasmid DNA Mediated by Electrotransfer

Abstract

The concept of DNA immunization was first advanced in the early 1990s, but was not developed because of an initial lack of efficiency. Recent technical advances in plasmid design and gene delivery techniques have allowed renewed interest in the idea. Particularly, a better understanding of genetic immunization has led to construction of optimized plasmids and the use of efficient molecular adjuvants. The field also took great advantage of new delivery techniques such as electrotransfer. This is a simple physical technique consisting of injecting plasmid DNA into a target tissue and applying an electric field, allowing up to a thousandfold more expression of the transgene than naked DNA. DNA immunization mediated by electrotransfer is now effective in a variety of preclinical models against infectious or acquired diseases such as cancer or autoimmune diseases, and is making its way through the clinics in several ongoing phase I human clinical trials. This review will briefly describe genetic immunization mediated by electrotransfer and the main fields of application.

Gene Electrotransfer: A Mechanistic Perspective

“…Additionally, specific T cells were detected in most of the patients which had from low to high dose. Other trials on humans using electroporation for the delivery of HIV, influenza, human papilloma virus and malaria vaccines have been performed or are ongoing [61, 62, 69]. The results confirm that human DNA vaccination using electroporation is safe and able to significantly elicit the immune response.…”

“…The idea behind genetic immunization simply consists of injecting a naked plasmid encoding a relevant antigen into muscle or skin that will produce antigens in sufficient amounts to initiate targeted immune response [61, 62]. This approach offers several advantages.…”

What you always needed to know about electroporation based DNA vaccines

“…Different approaches for optimizing the immunological response after a DNA vaccination are under investigation, covering aspects such as conjugates or molecular adjuvants, often in combination with exploitation of physical methods to improve the cellular uptake of the plasmid. 2 A well-known physical technique is electroporation, which is a *Correspondence to: Julie Gehl; Email: Julie.gehl@regionh.dk Submitted: 06/12/12; Revised: 08/24/12; Accepted: 09/02/12 http://dx.doi.org/10.4161/hv.22062 vaccinations are increasingly used to fight infectious disease, and DNA vaccines offer considerable advantages, including broader possibilities for vaccination and lack of need for cold storage. it has been amply demonstrated, that electroporation augments uptake of DNA in both skin and muscle, and it is foreseen that future DNA vaccination may to a large extent be coupled with and dependent upon electroporation based delivery.…”

An improved and robust DNA immunization method to develop antibodies against extra-cellular loops of multi-transmembrane proteins

“…26,27 Intramuscular injection of DNA, followed by site-specific in vivo electroporation, has also been described as an effective method to produce monoclonal antibodies. 28 While this method has been previously shown elsewhere to be successful in generating a specific immune response, we have observed otherwise, e.g., consistently lower levels of protein expression with this method, or the need to extend the immunization timeline to achieve an optimal immune response (Vij R and Hongo J, et al, unpublished results). The HTV injection method has been used to express high levels of protein in the liver for vaccination and mouse model development, 29 and to induce protective immunity.…”