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

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.
AuthorsMahamoud Sama Cherif, Mohammed Nasir Shuaibu, Yukinobu Kodama, Tomoaki Kurosaki, Gideon Kofi Helegbe, Mihoko Kikuchi, Akitoyo Ichinose, Tetsuo Yanagi, Hitoshi Sasaki, Katsuyuki Yui, Nguyen Huy Tien, Juntra Karbwang, Kenji Hirayama
JournalVaccine (Vaccine) Vol. 32 Issue 17 Pg. 1998-2006 (Apr 07 2014) ISSN: 1873-2518 [Electronic] Netherlands
PMID24440206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Recombinant Proteins
  • Vaccines, DNA
  • poly(gamma-glutamic acid)
  • Interleukin-12
  • Polyglutamic Acid
  • Interferon-gamma
  • Polyethyleneimine
Topics
  • 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, immunology)
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Plasmodium yoelii (immunology)
  • Polyethyleneimine (chemistry)
  • Polyglutamic Acid (analogs & derivatives, chemistry)
  • Protozoan Proteins (immunology)
  • Recombinant Proteins (immunology)
  • Spleen (cytology, immunology)
  • T-Lymphocytes (immunology)
  • Vaccines, DNA (immunology)

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