We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8 HLA-A03-11 supertypes-restricted epitopes from antigens expressed during '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. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against . Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8 T cells to produce IFN-γ. Self-assembling protein nanoparticle-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 major histocompatibility complex 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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627305 | PMC |
http://dx.doi.org/10.1038/s41541-017-0024-6 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!