Protein nanovaccine confers robust immunity against Toxoplasma
El Bissati K, Zhou Y, Paulillo SM, Raman SK, Karch CP, Roberts CW, Lanar DE, Reed S, Fox C, Carter D, Alexander J, Sette A, Sidney J, Lorenzi H, Begeman IJ, Burkhard P, McLeod R
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.