title: Effect of nanoparticle coating on the immunogenicity of plasmid DNA vaccine encoding P. yoelii MSP-1 C-terminal.
abstract: In order to assess a new strategy for DNA vaccine formulation and delivery, plasmid encoding Plasmodium yoelii MSP-1 C-terminal was formulated with newly designed nanoparticle-an anionic ternary complex of polyethylenimine and γ-polyglutamic acid (pVAX-MSP-1/PEI/γ-PGA), and intravenously administered to C57BL/6 mice in four different doses, three times at 3-week interval. Antibody response as determined by ELISA, IFA and Western blot, was dose-dependent and subsequent challenge with 10(5)P. yoelii-infected red blood cells revealed 33-60% survival in repeated experiments at a dose of 80 μg pDNA/mouse. IgG subtypes and cytokine levels in the serum and culture supernatants of stimulated spleen cells were also measured. Antigen-specific IgG response provoked by the DNA vaccination was dominated by IgG1 and IgG2b. Although the elevation of IL-12p40 and IFN-γ was marginal (P≥0.354) in the coated group, interleukin-4 levels were significantly higher (P≥0.013) in the coated group than in the naked or control group, suggesting a predominant Th2-type CD4(+) T cell response. These results therefore, overall indicate the possibility of selection and optimization of DNA vaccine formulation for intravenous delivery and may be useful in designing a nanoparticle-coated DNA vaccine that could optimally elicit a desired antibody response for various disease conditions.
authors.affiliation: Department of Immunogenetics, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: M N
authors.initials: MN
authors.lastname: Shuaibu
authors.forename: M S
authors.initials: MS
authors.lastname: Cherif
authors.forename: T
authors.initials: T
authors.lastname: Kurosaki
authors.forename: G K
authors.initials: GK
authors.lastname: Helegbe
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Yanagi
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood; D007275:Injections, Intravenous; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D004337:Drug Carriers; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D019444:Vaccines, DNA