title: Electroporation mediated DNA vaccination directly to a mucosal surface results in improved immune responses.
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.
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Gleb
authors: G
authors: Kichaev
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Janess M
authors: JM
authors: Mendoza
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Dinah
authors: D
authors: Amante
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Trevor R F
authors: TR
authors: Smith
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Jay R
authors: JR
authors: McCoy
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Niranjan Y
authors: NY
authors: Sardesai
authors: Inovio Pharmaceuticals Inc.;Blue Bell, PA USA.
authors: Kate E
authors: KE
authors: Broderick
mesh_terms: D058956:Administration, Mucosal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018274:Electroporation / Q000379:methods*; D005260:Female; D006168:Guinea Pigs; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*; D014621:Vagina / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D019444:Vaccines, DNA
keywords: DNA vaccine; direct mucosal; electroporation; intradermal
references: Biochem Biophys Res Commun. 1996 Mar 27;220(3):633-6
references: 8607816
references: Curr Opin Immunol. 2011 Jun;23(3):421-9
references: 21530212
references: Expert Opin Biol Ther. 2008 Nov;8(11):1645-57
references: 18847301
references: Curr Top Microbiol Immunol. 2012;354:157-79
references: 21203884
references: Nat Rev Immunol. 2003 Jan;3(1):63-72
references: 12511876
references: Immunology. 1996 May;88(1):147-52
references: 8707342
references: Hum Vaccin Immunother. 2013 Oct;9(10):2246-52
references: 24051434
references: J Immunol. 2007 Oct 1;179(7):4741-53
references: 17878373
references: Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):483-8
references: 12010863
references: Vaccine. 2011 Sep 9;29(39):6771-80
references: 21199706
references: Vaccine. 2006 May 22;24(21):4667-70
references: 16162367
references: Biophys Chem. 1987 May 9;26(2-3):321-35
references: 3607233
references: AIDS. 2002 Sep 6;16(13):1731-41
references: 12218383
references: Vaccine. 1997 Jun;15(8):811-3
references: 9234521
references: Biophys J. 1994 Feb;66(2 Pt 1):524-31
references: 8161705
references: DNA Cell Biol. 1993 Nov;12(9):785-9
references: 8216849
references: Sci Transl Med. 2012 Oct 10;4(155):155ra138
references: 23052295
references: Biophys Chem. 1984 May;19(3):211-25
references: 6722274
references: Int J Pharm. 2008 Aug 6;360(1-2):164-70
references: 18573624
references: Hum Gene Ther. 2010 Mar;21(3):357-62
references: 19839722
references: Vaccine. 2010 Jul 5;28(30):4827-36
references: 20451642
references: Curr Opin Immunol. 1993 Aug;5(4):484-91
references: 8216922
references: Vaccine. 2008 Sep 19;26(40):5073-4
references: 18652867
references: PLoS One. 2011 Apr 29;6(4):e19181
references: 21559474
references: J Virol. 2000 Dec;74(24):11598-607
references: 11090158
references: Gene Ther. 2011 Mar;18(3):258-65
references: 20962869
references: J Infect Dis. 1999 May;179 Suppl 3:S448-53
references: 10099117
references: J Virol. 2008 Jun;82(11):5643-9
references: 18353952
references: Immunol Lett. 2003 Dec 15;90(2-3):67-70
references: 14687705
references: Vaccine. 2012 Nov 6;30(48):6946-54
references: 22406460
references: Immunol Rev. 2011 Jan;239(1):62-84
references: 21198665
references: Gene Ther. 2007 Feb;14(3):275-80
references: 16988718
references: Vaccine. 2010 Sep 7;28(39):6445-54
references: 20670907
references: J Immunol. 2001 May 15;166(10):6257-65
references: 11342649
references: J Immunol. 2000 May 1;164(9):4635-40
references: 10779767
references: Annu Rev Immunol. 1997;15:617-48
references: 9143702
references: Biochim Biophys Acta. 2002 Aug 15;1572(1):1-9
references: 12204326
references: Vaccine. 1997 Jun;15(8):821-5
references: 9234524