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

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 gamma-polyglutamic acid (pVAX-MSP-1/PEI/gamma-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 mu g 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-gamma 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. (C) 2011 Elsevier Ltd. All rights reserved.