title: Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in Mice.
abstract: The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra , 3004-0504 Coimbra, Portugal.|Faculty of Pharmacy, University of Coimbra , Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Lebre
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne , Quai Ernest Ansermet 30, 1211 Geneva, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Borchard
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra , 3004-0504 Coimbra, Portugal.|Department of Life Sciences, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: H
authors.initials: H
authors.lastname: Faneca
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra , 3004-0504 Coimbra, Portugal.|Department of Life Sciences, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: M C
authors.initials: MC
authors.lastname: Pedroso de Lima
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra , 3004-0504 Coimbra, Portugal.|Faculty of Pharmacy, University of Coimbra , Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: O
authors.initials: O
authors.lastname: Borges
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014612:Vaccines
chemical_list: D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D014612:Vaccines; D004247:DNA; D048271:Chitosan
keywords: DNA vaccine; chitosan nanoparticles; gene delivery; hepatitis B vaccine; nasal immunization