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

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

Author information

1
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan; Institut National de Santé Publique, Université de Conakry, Guinea.
2
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
3
Department of Hospital Pharmacy, Nagasaki University, Japan.
4
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
5
Electron Microscopy Central Laboratory, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
6
Animal Research Center for Tropical Medicine, Nagasaki, Japan.
7
Department of Hospital Pharmacy, Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
8
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
9
Department of Product Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
10
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan. Electronic address: hiraken@nagasaki-u.ac.jp.

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)

PMID:
24440206
DOI:
10.1016/j.vaccine.2014.01.005
[Indexed for MEDLINE]
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