| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2402371 | Vaccine | 2006 | 9 Pages |
•Previously, PyTAM DNA vaccine was partially protective with low antibody production.•PEI and γ-PGA complex as delivery system could augment PyTAM protective immune response by increasing DCs activation and concomitant induction of IL-12 and IFN-γ in immunized mice.•Using mouse anti-PyTAM antibody, PyTAM was revealed to be expressed in the schizont stage parasite and located on the parasitophorous vacuole.
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.
Graphical abstractFormation of NP formulated PyTAM plasmid DNA and NP formulated empty plasmid DNA with negative ζ-potential. Study design and survival curve: Three group of mice were immunized with either NP formulated PyTAM plasmid DNA, naked TAM plasmid DNA or NP formulated empty plasmid DNA. Mice were immunized three times at three weeks interval then challenged with lethal P. yoelii 17xl two weeks after the last boost.Figure optionsDownload full-size imageDownload as PowerPoint slide
