Protein nanovaccine confers robust immunity against Toxoplasma

El Bissati, Kamal and Zhou, Ying and Paulillo, Sara M. and Raman, Senthil K. and Karch, Christoper P. and Roberts, Craig W. and Lanar, David E. and Steve, Reed and Fox, Chris and Carter, Darrick and Alexander, Jeff and Sette, Alessandro and Sidney, John and Lorenzi, Hernan and Begeman, Ian J. and Burkhard, Peter and McLeod, Rima (2017) Protein nanovaccine confers robust immunity against Toxoplasma. npj Vaccines, 2. 24. ISSN 2059-0105

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    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.