Optimization of Electroporation-Enhanced Intradermal Delivery of DNA Vaccine Using a Minimally Invasive Surface Device

Abstract

In vivo electroporation (EP) is an efficient nonviral method for enhancing DNA vaccine delivery and immunogenicity in animals and humans. Intradermal delivery of DNA vaccines is an attractive strategy because of the immunocompetence of skin tissue. We have previously reported a minimally invasive surface intradermal EP (SEP) device for delivery of prophylactic DNA vaccines. Robust antibody responses were induced after vaccine delivery via surface EP in several tested animal models. Here we further investigated the optimal EP parameters for efficient delivery of DNA vaccines, with a specific emphasis on eliciting cellular immunity in addition to robust humoral responses. In a mouse model, using applied voltages of 10-100 V, transgene expression of green fluorescent protein and luciferase reporter genes increased significantly when voltages as low as 10 V were used as compared with DNA injection only. Tissue damage to skin was undetectable when voltages of 20 V and less were applied. However, inflammation and bruising became apparent at voltages above 40 V. Delivery of DNA vaccines encoding influenza virus H5 hemagglutinin (H5HA) and nucleoprotein (NP) of influenza H1N1 at applied voltages of 10-100 V elicited robust and sustained antibody responses. In addition, low-voltage (less than 20 V) EP elicited higher and more sustained cellular immune responses when compared with the higher voltage (above 20 V) EP groups after two immunizations. The data confirm that low-voltage EP, using the SEP device, is capable of efficient delivery of DNA vaccines into the skin, and establishes that these parameters are sufficient to elicit both robust and sustainable humoral as well as cellular immune responses without tissue damage. The SEP device, functioning within these parameters, may have important clinical applications for delivery of prophylactic DNA vaccines against diseases such as HIV infection, malaria, and tuberculosis that require both cellular and humoral immune responses for protection.

Molecular and immunological characterization of a DNA-launched yellow fever virus 17D infectious clone

“…Furthermore, novel DNA formulations and delivery routes could be explored to achieve better immunogenicity and acceptability. Although the electroporation method used in this study has been widely tested in a broad range of animals and has shown promising results in human clinical trials with DNA vaccines (Kopycinski et al, 2012;Vasan et al, 2011), intradermal electroporation delivery of DNA vaccines has started to attract more attention, owing to the accessibility of the skin and the abundance of antigenpresenting cells in the epidermis and dermis (Bråve et al, 2010(Bråve et al, , 2011Lin et al, 2012). With the advances in DNA formulation and delivery technologies, the DNA-launched YFV-17D vaccine may prove to be a stable, facile-toproduce and effective alternative for the current YFV liveattenuated vaccine, and further holds promise as a platform for the development of YFV-17D-based recombinant DNA vaccines.…”

Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques

“…54 Here, we directly compared the immune responses induced upon IM IM/EP immunized animals showed robust responses with a frequency of 0.1-0.6% of Env-specific IFN-γ + T cells (Fig. 8A).…”

Engineering Approaches to Transdermal Drug Delivery: A Tribute to Contributions of Prof. Robert Langer

“…These include small molecules such as methotrexate [101,102] and lidocaine [103], among others [15]. Several macromolecules have also been delivered using electroporation including heparin [99], insulin [104,105] and vaccines [106,107]. Electroporation has been particularly effective in delivering DNA vaccines owing to the unique ability of electroporation to enhance transport across the stratum corneum as well as cell membranes [107,108].…”

“…Several macromolecules have also been delivered using electroporation including heparin [99], insulin [104,105] and vaccines [106,107]. Electroporation has been particularly effective in delivering DNA vaccines owing to the unique ability of electroporation to enhance transport across the stratum corneum as well as cell membranes [107,108]. Electroporation-mediated DNA delivery of vaccines has yielded excellent immune responses in animals [106,109].…”