title: Intranasal Immunization with DOTAP Cationic Liposomes Combined with DC-Cholesterol Induces Potent Antigen-Specific Mucosal and Systemic Immune Responses in Mice.
abstract: Despite the progress made by modern medicine, infectious diseases remain one of the most important threats to human health. Vaccination against pathogens is one of the primary methods used to prevent and treat infectious diseases that cause illness and death. Vaccines administered by the mucosal route are potentially a promising strategy to combat infectious diseases since mucosal surfaces are a major route of entry for most pathogens. However, this route of vaccination is not widely used in the clinic due to the lack of a safe and effective mucosal adjuvant. Therefore, the development of safe and effective mucosal adjuvants is key to preventing infectious diseases by enabling the use of mucosal vaccines in the clinic. In this study, we show that intranasal administration of a cationic liposome composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposome) has a potent mucosal adjuvant effect in mice. Intranasal vaccination with ovalbumin (OVA) in combination with DOTAP/DC-chol liposomes induced the production of OVA-specific IgA in nasal tissues and increased serum IgG1 levels, suggesting that the cationic DOTAP/DC-chol liposome leads to the induction of a Th2 immune response. Additionally, nasal-associated lymphoid tissue and splenocytes from mice treated with OVA plus DOTAP/DC-chol liposome showed high levels of IL-4 expression. DOTAP/DC-chol liposomes also enhanced OVA uptake by CD11c+ dendritic cells in nasal-associated lymphoid tissue. These data demonstrate that DOTAP/DC-chol liposomes elicit immune responses via an antigen-specific Th2 reaction. These results suggest that cationic liposomes merit further development as a mucosal adjuvant for vaccination against infectious diseases.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Tada
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hidaka
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwase
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamakita
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Muto
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Sato
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takayama
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Honjo
authors.affiliation: Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000276:immunology*; D007110:Immunity, Active / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology*; D000644:Quaternary Ammonium Compounds / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D015847:Interleukin-4; D010047:Ovalbumin; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane