Non-contact helium-based plasma for delivery of DNA vaccines

Abstract

Non-viral in vivo administration of plasmid DNA for vaccines and immunotherapeutics has been hampered by inefficient delivery. Methods to enhance delivery such as in vivo electroporation (EP) have demonstrated effectiveness in circumventing this difficulty. However, the contact-dependent nature of EP has resulting side effects in animals and humans. Noncontact delivery methods should, in principle, overcome some of these obstacles. This report describes a helium plasma–based delivery system that enhanced humoral and cellular antigen-specific immune responses in mice against an intradermally administered HIV gp120-expressing plasmid vaccine (pJRFLgp120). The most efficient plasma delivery parameters investigated resulted in the generation of geometric mean antibody-binding titers that were 19-fold higher than plasmid delivery alone. Plasma mediated delivery of pJRFLgp120 also resulted in a 17-fold increase in the number of interferon-gamma spot-forming cells, a measure of CD8+ cytotoxic T cells, compared with non-facilitated plasmid delivery. This is the first report demonstrating the ability of this contact-independent delivery method to enhance antigen-specific immune responses against a protein generated by a DNA vaccine.

Keywords: :

• CTL responses
• DNA vaccine
• HIV
• antibody responses
• helium plasma

Conflicts of Interest

Richard Connolly, Mark Jaroszeski, and Andrew Hoff are inventors on patent applications involving the technology utilized in this study. Additionally, Mark Jaroszeski holds stock options in Inovio Pharmaceuticals, Inc., a company whose major emphasis is the development of electrical delivery technologies. None of the other co-authors of the work declare any conflicts of interest.

Acknowledgments

The study described in this paper was supported, in part, by grant AI079706 from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID. In addition, the work was also supported, in part, by a pilot grant from the Florida Center of Excellence in Biomolecular Identification and Targeted Therapeutics (FCoE-BITT). We also acknowledge Dr. David Weiner and Dr. Jian Yan, from the University of Pennsylvania, for generously supplying the JRFLgp120 expressing DNA plasmid. Joseph Register of the University of South Florida provided photographic support (Fig. 1B). We would like to acknowledge Pamela Fried and Diana Winters from Drexel University College of Medicine Academic Publishing Services for their editorial, formatting and journal submission expertise.