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

We created and tested multi- epitopeDNA or protein vaccines with TLR4 ligand emulsion adjuvant(gluco glucopyranosyl lipid adjuvantin a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondiiin 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- epitopevaccines 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 presentationof the antigens must account for the immunogenicity of our adjuvantedprotein. Thus, our work creates an adjuvantedplatform assembly of peptides resulting in cross presentationof CD8(+) T cell-eliciting epitopesin a vaccine that prevents toxoplasmosis.