title: pH-sensitive carbonate apatite nanoparticles as DNA vaccine carriers enhance humoral and cellular immunity.
abstract: To demonstrate the potential of pH-sensitive carbonate apatite (CO₃Ap) nanoparticles as DNA vaccine carriers to enhance vaccination efficacy, we examined the humoral and cellular immune responses of C57BL/6 mice immunized with the plasmid expression vector pCI-neo encoding the full-length soluble ovalbumin (OVA) (pCI-neo-sOVA), pCI-neo-sOVA/CO₃Ap complexes, or pCI-neo/CO₃Ap complexes as a control. Mice immunized with a low dose of pCI-neo-sOVA-loaded CO₃Ap (10 μg) produced ex vivo splenocyte proliferation after stimulation with CD8 T-cell but not CD4 T-cell epitopes and a delayed-type-hypersensitivity reaction more efficiently than mice in the other groups. Furthermore, mice receiving this immunization generated the same levels of OVA-specific antibodies and interferon (IFN)-γ secretion after CD8 T-cell and CD4 T-cell epitope challenges as those in mice treated with 100 μg of free pCI-neo-sOVA, whereas mice injected with a high dose of pCI-neo-sOVA-loaded CO₃Ap (100 μg) or with control plasmids produced negligible levels of OVA-specific antibodies or IFN-γ. Therefore, our results showed that 10 μg of pCI-neo-sOVA delivered by CO₃Ap strongly elicited humoral and cellular immune responses. This study is the first to demonstrate the promising potential of CO₃Ap nanoparticles for DNA vaccine delivery.
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Pan
authors.initials: P
authors.lastname: He
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Shin-nosuke
authors.initials: SN
authors.lastname: Takeshima
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tada
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4252 Nagatsuka-cho, Midoriku, Yokohama 226-8501, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: aida@riken.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000737:chemistry / Q000276:immunology*
chemical_list: D001031:Apatites; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; C030782:carboapatite; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Antibody; Cellular immunity; DNA vaccine carrier; Nanoparticle; pH-sensitive carbonate apatite