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Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii

El Bissati, Kamal and Chentoufi, Aziz A and Krishack, Paulette A and Zhou, Ying and Woods, Stuart and Dubey, Jitender P and Vang, Lo and Lykins, Joseph and Broderick, Kate E and Mui, Ernest and Suzuki, Yasuhiro and Sa, Qila and Bi, Stephanie and Cardona, Nestor and Verma, Shiv K and Frazeck, Laura and Reardon, Catherine A and Sidney, John and Alexander, Jeff and Sette, Alessandro and Vedvick, Tom and Guderian, Jeffrey A and Reed, Steven and Roberts, Craig W (2016) Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii. JCI Insight, 1 (15). ISSN 2379-3708

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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.