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.
Authors
Kamal El Bissati, Aziz A. Chentoufi, Paulette A. Krishack, Ying Zhou, Stuart Woods, Jitender P. Dubey, Lo Vang, Joseph Lykins, Kate E. Broderick, Ernest Mui, Yasuhiro Suzuki, Qila Sa, Stephanie Bi, Nestor Cardona, Shiv K. Verma, Laura Fraczek, Catherine A. Reardon, John Sidney, Jeff Alexander, Alessandro Sette, Tom Vedvick, Chris Fox, Jeffrey A. Guderian, Steven Reed, Craig W. Roberts, Rima McLeod
Figure 5
Multivalent polypeptide LO and AZ protective efficacy in vivo with HLA-A*11:01 transgenic mice survival curve after challenge with Type II parasites.
