El Bissati K1,
Chentoufi AA2,
Krishack PA3,
Zhou Y1,
Woods S4,
Dubey JP5,
Vang L6,
Lykins J1,
Broderick KE7,
Mui E1,
Suzuki Y8,
Sa Q8,
Bi S1,
Cardona N1,
Verma SK5,
Frazeck L1,
Reardon CA3,
Sidney J9,
Alexander J6,
Sette A9,
Vedvick T10,
Fox C10,
Guderian JA10,
Reed S10,
Roberts CW4,
McLeod R1.
Abstract
We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8+ T cell-eliciting epitopes, a universal CD4+ helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8+ T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8+ T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis.
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