Effect of nanoparticle coating on the immunogenicity of plasmid DNA vaccine encoding P. yoelii MSP-1 C-terminal

• Published in: Vaccine 2011-04, Vol.29 (17), p.3239-3247
• Main Authors: Shuaibu, M.N, Cherif, M.S, Kurosaki, T, Helegbe, G.K, Kikuchi, M, Yanagi, T, Sasaki, H, Hirayama, K
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Protozoan - blood; blood serum; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; coatings; Cytokines; Cytokines - secretion; DNA vaccination; Drug Carriers - administration & dosage; Drug Carriers - chemistry; enzyme-linked immunosorbent assay; erythrocytes; Female; IgG subtypes; immune response; Immunoassay; immunoglobulin G; Immunoglobulin G - blood; Injections, Intravenous; interferon-gamma; interleukin-4; Intravenous; intravenous injection; Malaria; Malaria - immunology; Malaria - prevention & control; Malaria Vaccines - administration & dosage; Malaria Vaccines - genetics; Malaria Vaccines - immunology; Merozoite Surface Protein 1 - genetics; Merozoite Surface Protein 1 - immunology; Mice; Mice, Inbred C57BL; Nanoparticle; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; plasmids; Plasmodium yoelii; Plasmodium yoelii - genetics; Plasmodium yoelii - immunology; polyglutamic acid; recombinant vaccines; splenocytes; Survival Analysis; Th2 Cells - immunology; vaccination; Vaccination - methods; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Western blotting
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.02.033

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 105 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.