Abstract
Particle-mediated DNA delivery technologies (“gene guns”) have been shown in both animal and clinical studies to be an effective means of increasing the immunogenicity and protective efficacy of DNA vaccines. The primary goal in optimizing particle-mediated epidermal delivery (PMED) vaccination in different animal models is to achieve delivery of DNA-coated gold beads into the viable epidermis. Two key para-meters that influence this outcome include the delivery pressure, which controls the penetrative force of the beads into the skin, and the anatomical site of DNA delivery. Although the ferret has been extensively used as an experimental model for influenza infection in humans, very few studies have investigated the capacity for PMED DNA vaccination to induce protective immune responses in ferrets. Here we describe methods to optimize DNA vaccine delivery using the PowderJect XR1 gene delivery in ferrets. We first assess the effects of firing pressure on both the delivery of DNA-coated gold beads into the desired epidermal layer and the degree of DNA vaccine reporter gene expression at the target site. Second, we evaluate the impact of vaccination site (skin or tongue) on DNA vaccine immunogenicity by measuring serum antibody responses to the model antigens influenza virus hemagglutinin and hepatitis B core antigen. Results from these studies support the use of the PowderJect XR1 device in ferrets for the study of prophylactic and therapeutic DNA vaccines against clinically important diseases such as influenza virus infection.
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References
Fuller DH, Loudon P, Schmaljohn C (2006) Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases. Methods 40:86–97
Payne LG, Fuller DH, Haynes JR (2002) Particle-mediated DNA vaccination of mice, monkeys and men: looking beyond the dogma. Curr Opin Mol Ther 4:459–466
Yager EJ, Dean HJ, Fuller DH (2009) Prospects for developing an effective particle-mediated DNA vaccine against influenza. Expert Rev Vaccines 8:1205–1220
Falo LD Jr (1999) Targeting the skin for genetic immunization. Proc Assoc Am Physicians 111:211–219
Falo LD Jr, Storkus WJ (1998) Giving DNA vaccines a helping hand. Nat Med 4:1239–1240
Bennett AM et al (1999) Gene gun mediated vaccination is superior to manual delivery for immunisation with DNA vaccines expressing protective antigens from Yersinia pestis or Venezuelan Equine Encephalitis virus. Vaccine 18:588–596
Huber VC, Thomas PG, McCullers JA (2009) A multi-valent vaccine approach that elicits broad immunity within an influenza subtype. Vaccine 27:1192–1200
Pertmer TM et al (1995) Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13:1427–1430
Roberts LK et al (2005) Clinical safety and efficacy of a powdered Hepatitis B nucleic acid vaccine delivered to the epidermis by a commercial prototype device. Vaccine 23:4867–4878
Drape RJ et al (2006) Epidermal DNA vaccine for influenza is immunogenic in humans. Vaccine 24:4475–4481
Jones S et al (2009) DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial. Vaccine 27:2506–2512
Fuller DH et al (1997) Enhancement of immunodeficiency virus-specific immune responses in DNA-immunized rhesus macaques. Vaccine 15:924–926
Fuller DH et al (2002) Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine. J Virol 76:3309–3317
Fuller DH et al (2006) DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued. Virology 348:200–215
Doria-Rose NA et al (2003) Multigene DNA priming-boosting vaccines protect macaques from acute CD4+-T-cell depletion after simian-human immunodeficiency virus SHIV89.6P mucosal challenge. J Virol 77:11563–11577
Eisenbraun MD, Fuller DH, Haynes JR (1993) Examination of parameters affecting the elicitation of humoral immune responses by particle bombardment-mediated genetic immunization. DNA Cell Biol 12:791–797
Fynan EF, Robinson HL, Webster RG (1993) Use of DNA encoding influenza hemagglutinin as an avian influenza vaccine. DNA Cell Biol 12:785–789
Macklin MD et al (1998) Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus. J Virol 72:1491–1496
Marini RP et al (2002) Biology and diseases of ferrets. In: Fox JG, Anderson LC, Loew FM, Quimby FW (eds) Laboratory animal medicine. Academic, San Diego, pp 483–517
Maher JA, DeStefano J (2004) The ferret: an animal model to study influenza virus. Lab Anim (NY) 33:50–53
Matsuoka Y, Lamirande EW, Subbarao K (2009) The ferret model for influenza. Curr Protoc Microbiol Chapter 15:Unit 15G 12
Loudon PT et al (2010) GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. PLoS One 5:e11021
Roy MJ et al (2000) Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine. Vaccine 19:764–778
Wang S, Joshi S, Lu S (2004) Delivery of DNA to skin by particle bombardment. Methods Mol Biol 245:185–196
Couch RB, Kasel JA (1983) Immunity to influenza in man. Annu Rev Microbiol 37:529–549
Kildsgaard J et al (2007) Sublingual immunotherapy in sensitized mice. Ann Allergy Asthma Immunol 98:366–372
Song JH et al (2008) Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc Natl Acad Sci USA 105:1644–1649
Cuburu N et al (2007) Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 25:8598–8610
Acknowledgments
This work was supported by U01 AI074509 from National Institute of Health/NIAID awarded to Deborah H. Fuller.
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Yager, E.J., Stagnar, C., Gopalakrishnan, R., Fuller, J.T., Fuller, D.H. (2013). Optimizing Particle-Mediated Epidermal Delivery of an Influenza DNA Vaccine in Ferrets. In: Sudowe, S., Reske-Kunz, A. (eds) Biolistic DNA Delivery. Methods in Molecular Biology, vol 940. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-110-3_19
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DOI: https://doi.org/10.1007/978-1-62703-110-3_19
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