Protein nanovaccine confers robust immunity against Toxoplasma

Kamal El Bissati, Ying Zhou, Sara M. Paulillo, Senthil K. Raman, Christoper P. Karch, Craig W. Roberts, David E. Lanar, Reed Steve, Chris Fox, Darrick Carter, Jeff Alexander, Alessandro Sette, John Sidney, Hernan Lorenzi, Ian J. Begeman, Peter Burkhard, Rima McLeod

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)
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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 languageEnglish
Article number24
Number of pages12
Journalnpj Vaccines
Publication statusPublished - 5 Sep 2017


  • Toxoplasma gondii
  • HLA-A03-11
  • vaccine
  • self-assembling protein nanoparticles


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