Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model

Vaccine. 2014 Apr 7;32(17):1998-2006. doi: 10.1016/j.vaccine.2014.01.005. Epub 2014 Jan 15.

Abstract

We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production.

Keywords: DNA vaccine; GPI8p-transamidase; Gamma polyglutamic acid (γ-PGA); Nanoparticle; Plasmodium yoelii; Polyethylimine (PEI).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Malaria / prevention & control*
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles*
  • Plasmodium yoelii / immunology*
  • Polyethyleneimine / chemistry
  • Polyglutamic Acid / analogs & derivatives
  • Polyglutamic Acid / chemistry
  • Protozoan Proteins / immunology*
  • Recombinant Proteins / immunology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Vaccines, DNA / immunology

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Recombinant Proteins
  • Vaccines, DNA
  • poly(gamma-glutamic acid)
  • Interleukin-12
  • Polyglutamic Acid
  • Interferon-gamma
  • Polyethyleneimine