Protein nanovaccine confers robust immunity against Toxoplasma

We designed and produced a self-assemblingprotein nanoparticle. This self-assemblingprotein nanoparticlecontains five CD8+ HLA-A03-11 supertypes-restricted epitopesfrom antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4+ T cell epitopePADRE, and flagellinas a scaffold and TLR5agonist. These CD8+ T cell epitopeswere separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assemblingprotein nanoparticleadjuvanted with TLR4ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responsesand protectionof HLA-A*1101 transgenic mice against T. gondii. Immunization, using self-assemblingprotein nanoparticle-GLA-SE, activated CD8+ T cells to produce IFN-γ. Self-assemblingprotein 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- epitopeprotein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex ClassI and II molecules. Furthermore, these results suggest that activation of TLR4and TLR5could be useful for development of vaccines that elicit T cells to prevent toxoplasmosisin humans.