A combination of intradermal jet-injection and electroporation overcomes in vivo dose restriction of DNA vaccines
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GENETIC VACCINES AND THERAPY
RESEARCH
Open Access
A combination of intradermal jet-injection and electroporation overcomes in vivo dose restriction of DNA vaccines David Hallengärd1*, Andreas Bråve2, Maria Isaguliants1, Pontus Blomberg3, Jenny Enger3, Richard Stout4, Alan King5 and Britta Wahren1
Abstract Background: The use of optimized delivery devices has been shown to enhance the potency of DNA vaccines. However, further optimization of DNA vaccine delivery is needed for this vaccine modality to ultimately be efficacious in humans. Methods: Herein we evaluated antigen expression and immunogenicity after intradermal delivery of different doses of DNA vaccines by needle or by the Biojector jet-injection device, with or without the addition of electroporation (EP). Results: Neither needle injection augmented by EP nor Biojector alone could induce higher magnitudes of immune responses after immunizations with a high dose of DNA. After division of a defined DNA dose into multiple skin sites, the humoral response was particularly enhanced by Biojector while cellular responses were particularly enhanced by EP. Furthermore, a close correlation between in vivo antigen expression and cell-mediated as well as humoral immune responses was observed. Conclusions: These results show that two optimized DNA vaccine delivery devices can act together to overcome dose restrictions of plasmid DNA vaccines. Keywords: DNA vaccine, Electroporation, Jet-injection, Biojector
Background Plasmid-based DNA vaccines are commonly used in vaccine research to induce immune responses against infectious agents or tumor antigens. These vaccines possess advantages including rapid construction and high stability, as well as the capacity to induce cellular immune responses owing to the intracellular production of the encoded antigen [1]. Still, further optimization of DNA vaccine delivery is needed for this vaccine modality to ultimately be efficacious in humans [2,3]. One strategy to influence the immune responses to DNA vaccines is by the choice of immunization route. We have chosen to employ intradermal (id) immunizations as the skin, unlike muscle tissue, has a large population of resident antigen presenting cells (APCs) that can facilitate * Correspondence: [email protected] 1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Nobels väg 16, 171 77, Stockholm, Sweden Full list of author information is available at the end of the article
the induction of vaccine-specific immune responses [4,5]. The skin is also a more accessible tissue than muscle, allowing for less painful DNA vaccine delivery and facilitating studies of in vivo protein expression. In addition to conventional needle immunization, several injection devices including Biojector and in vivo electroporation (EP) are being used to improve DNA delivery to the skin. Biojector is a CO2-propelled needle-free device that injects DNA plasmids as a highly focused liquid stream into the skin. This has been shown to enhance antigen expression as compared to co
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