Electroporation Mediated DNA Vaccination Directly to a Mucosal Surface Results in Improved Immune Responses

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2013 Aug 20

PMID 23954979

Citations 13

Authors

Gleb Kichaev

Janess M Mendoza

Dinah Amante

Trevor R F Smith

Jay R McCoy

Niranjan Y Sardesai

Kate E Broderick

Affiliations

Soon will be listed here.

Abstract

In vivo electroporation (EP) has been shown to be a highly efficient non-viral method for enhancing DNA vaccine delivery and immunogenicity, when the site of immunization is the skin or muscle of animals and humans. However, the route of entry for many microbial pathogens is via the mucosal surfaces of the human body. We have previously reported on minimally invasive, surface and contactless EP devices for enhanced DNA delivery to dermal tissue. Robust antibody responses were induced following vaccine delivery in several tested animal models using these devices. Here, we investigated extending the modality of the surface device to efficiently deliver DNA vaccines to mucosal tissue. Initially, we demonstrated reporter gene expression in the epithelial layer of buccal mucosa in a guinea pig model. There was minimal tissue damage in guinea pig mucosal tissue resulting from EP. Delivery of a DNA vaccine encoding influenza virus nucleoprotein (NP) of influenza H1N1 elicited robust and sustained systemic IgG antibody responses following EP-enhanced delivery in the mucosa. Upon further analysis, IgA antibody responses were detected in vaginal washes and sustained cellular immune responses were detected in animals immunized at the oral mucosa with the surface EP device. This data confirms that DNA delivery and EP targeting mucosal tissue directly results in both robust and sustainable humoral as well as cellular immune responses without tissue damage. These responses are seen both in the mucosa and systemically in the blood. Direct DNA vaccine delivery enhanced by EP in mucosa may have important clinical applications for delivery of prophylactic and therapeutic DNA vaccines against diseases such as HIV, HPV and pneumonia that enter at mucosal sites and require both cellular and humoral immune responses for protection.

Citing Articles

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References

Zhang L, Li L, Hoffmann G, Hoffman R . Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: an approach to gene therapy of skin aging and other diseases. Biochem Biophys Res Commun. 1996; 220(3):633-6. DOI: 10.1006/bbrc.1996.0455. View

Sardesai N, Weiner D . Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol. 2011; 23(3):421-9. PMC: 3109217. DOI: 10.1016/j.coi.2011.03.008. View

Chiarella P, Massi E, De Robertis M, Sibilio A, Parrella P, Fazio V . Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration. Expert Opin Biol Ther. 2008; 8(11):1645-57. DOI: 10.1517/14712598.8.11.1645. View

Belyakov I, Ahlers J . Mucosal immunity and HIV-1 infection: applications for mucosal AIDS vaccine development. Curr Top Microbiol Immunol. 2011; 354:157-79. DOI: 10.1007/82_2010_119. View

Fagarasan S, Honjo T . Intestinal IgA synthesis: regulation of front-line body defences. Nat Rev Immunol. 2003; 3(1):63-72. DOI: 10.1038/nri982. View

Eriksson K, Ahlfors E, Kaiserlian D, Czerkinsky C . Antigen presentation in the murine oral epithelium. Immunology. 1996; 88(1):147-52. PMC: 1456467. DOI: 10.1046/j.1365-2567.1996.d01-647.x. View

Diehl M, Lee J, Daniels S, Tebas P, Khan A, Giffear M . Tolerability of intramuscular and intradermal delivery by CELLECTRA(®) adaptive constant current electroporation device in healthy volunteers. Hum Vaccin Immunother. 2013; 9(10):2246-52. PMC: 3906411. DOI: 10.4161/hv.24702. View

Ahlen G, Soderholm J, Tjelle T, Kjeken R, Frelin L, Hoglund U . In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J Immunol. 2007; 179(7):4741-53. DOI: 10.4049/jimmunol.179.7.4741. View

Kadish A, Timmins P, Wang Y, Ho G, Burk R, Ketz J . Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol Biomarkers Prev. 2002; 11(5):483-8. View

10.

Lin F, Shen X, McCoy J, Mendoza J, Yan J, Kemmerrer S . A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle. Vaccine. 2011; 29(39):6771-80. DOI: 10.1016/j.vaccine.2010.12.057. View

11.

Tjelle T, Salte R, Mathiesen I, Kjeken R . A novel electroporation device for gene delivery in large animals and humans. Vaccine. 2005; 24(21):4667-70. DOI: 10.1016/j.vaccine.2005.08.068. View

12.

Sugar I, Forster W, Neumann E . Model of cell electrofusion. Membrane electroporation, pore coalescence and percolation. Biophys Chem. 1987; 26(2-3):321-35. DOI: 10.1016/0301-4622(87)80033-9. View

13.

Clerici M, Barassi C, Devito C, Pastori C, Piconi S, Trabattoni D . Serum IgA of HIV-exposed uninfected individuals inhibit HIV through recognition of a region within the alpha-helix of gp41. AIDS. 2002; 16(13):1731-41. DOI: 10.1097/00002030-200209060-00004. View

14.

Ban E, van Ginkel F, Simecka J, Kiyono H, Robinson H, McGhee J . Mucosal immunization with DNA encoding influenza hemagglutinin. Vaccine. 1997; 15(8):811-3. DOI: 10.1016/s0264-410x(96)00263-0. View

15.

Wolf H, Rols M, Boldt E, Neumann E, Teissie J . Control by pulse parameters of electric field-mediated gene transfer in mammalian cells. Biophys J. 1994; 66(2 Pt 1):524-31. PMC: 1275719. DOI: 10.1016/s0006-3495(94)80805-7. View

16.

Fynan E, Robinson H, Webster R . Use of DNA encoding influenza hemagglutinin as an avian influenza vaccine. DNA Cell Biol. 1993; 12(9):785-9. DOI: 10.1089/dna.1993.12.785. View

17.

Bagarazzi M, Yan J, Morrow M, Shen X, Parker R, Lee J . Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012; 4(155):155ra138. PMC: 4317299. DOI: 10.1126/scitranslmed.3004414. View

18.

Sugar I, Neumann E . Stochastic model for electric field-induced membrane pores. Electroporation. Biophys Chem. 1984; 19(3):211-25. DOI: 10.1016/0301-4622(84)87003-9. View

19.

Kanazawa T, Takashima Y, Hirayama S, Okada H . Effects of menstrual cycle on gene transfection through mouse vagina for DNA vaccine. Int J Pharm. 2008; 360(1-2):164-70. DOI: 10.1016/j.ijpharm.2008.04.038. View

20.

Heller R, Cruz Y, Heller L, Gilbert R, Jaroszeski M . Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode array. Hum Gene Ther. 2009; 21(3):357-62. PMC: 2865213. DOI: 10.1089/hum.2009.065. View