Abstract
We designed and produced a self-assembling protein nanoparticle (SAPN). This SAPN contains five CD8+ HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4+ T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8+ T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. SAPN adjuvanted with TLR4 ligand-emulsion GLA-SE (SAPN-GLA-SE) were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against T. gondii. Immunization, using SAPN-GLA-SE, activated CD8+ T cells to produce IFN-γ. SAPN-GLA-SE also protected HLA- A*1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8+ T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by MHC Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.
Original language | English |
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Article number | 24 |
Number of pages | 12 |
Journal | npj Vaccines |
Volume | 2 |
DOIs | |
Publication status | Published - 5 Sep 2017 |
Keywords
- Toxoplasma gondii
- HLA-A03-11
- vaccine
- self-assembling protein nanoparticles