title: Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor.
abstract: Skin represents an attractive target for DNA vaccine delivery because of its natural richness in APCs, whose targeting may potentiate the effect of vaccination. Nevertheless, intramuscular electroporation is the most common delivery method for ECTM vaccination. In this study we assessed whether intradermal administration could deliver the vaccine into different cell types and we analyzed the evolution of tissue infiltrate elicited by the vaccination protocol. Intradermal electroporation (EP) vaccination resulted in transfection of different skin layers, as well as mononuclear cells. Additionally, we observed a marked recruitment of reactive infiltrates mainly 6-24 hours after treatment and inflammatory cells included CD11c(+). Moreover, we tested the efficacy of intradermal vaccination against Her2/neu antigen in cellular and humoral response induction and consequent protection from a Her2/neu tumor challenge in Her2/neu nontolerant and tolerant mice. A significant delay in transplantable tumor onset was observed in both BALB/c (p ≤ 0,0003) and BALB-neuT mice (p = 0,003). Moreover, BALB-neuT mice displayed slow tumor growth as compared to control group (p < 0,0016). In addition, while in vivo cytotoxic response was observed only in BALB/c mice, a significant antibody response was achieved in both mouse models. Our results identify intradermal EP vaccination as a promising method for delivering Her2/neu DNA vaccine.
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Lamolinara
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy ; Department of Medicine, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stramucci
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy.
authors.forename: Albana
authors.initials: A
authors.lastname: Hysi
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.affiliation: Department of Bioscience and Biotechnology, University of Camerino, Camerino, 63100 Macerata, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Mariotti
authors.affiliation: Department of Bioscience and Biotechnology, University of Camerino, Camerino, 63100 Macerata, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
authors.affiliation: Aging Research Center, G. d'Annunzio University, 66100 Chieti, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Curcio
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D018274:Electroporation; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA