Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.
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.
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.
Mahamoud Sama
MS
Cherif
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
Mohammed Nasir
MN
Shuaibu
Department of Hospital Pharmacy, Nagasaki University, Japan.
Yukinobu
Y
Kodama
Department of Hospital Pharmacy, Nagasaki University, Japan.
Tomoaki
T
Kurosaki
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
Gideon Kofi
GK
Helegbe
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
Mihoko
M
Kikuchi
Electron Microscopy Central Laboratory, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
Akitoyo
A
Ichinose
Animal Research Center for Tropical Medicine, Nagasaki, Japan.
Tetsuo
T
Yanagi
Department of Hospital Pharmacy, Nagasaki University, Japan; Global COE Program, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan.
Hitoshi
H
Sasaki
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
Katsuyuki
K
Yui
Department of Product Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Nguyen Huy
NH
Tien
Department of Product Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Juntra
J
Karbwang
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.
Kenji
K
Hirayama
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010967:Plasmodium yoelii / Q000276:immunology*; D011094:Polyethyleneimine / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C511775:poly(gamma-glutamic acid); D018664:Interleukin-12; D011099:Polyglutamic Acid; D007371:Interferon-gamma; D011094:Polyethyleneimine
DNA vaccine; GPI8p-transamidase; Gamma polyglutamic acid (γ-PGA); Nanoparticle; Plasmodium yoelii; Polyethylimine (PEI)