1. Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii
- Author
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Steven G. Reed, Kamal El Bissati, Qila Sa, Tom Vedvick, Rima McLeod, Lo Vang, Alessandro Sette, Kate E Broderick, Nestor Cardona, Jeff Alexander, Yasuhiro Suzuki, Aziz Alami Chentoufi, Jitender P. Dubey, Catherine A. Reardon, Stephanie Bi, Ying Zhou, Jeffrey A. Guderian, Joseph Lykins, John Sidney, Craig W. Roberts, Laura Fraczek, Stuart Woods, Paulette A. Krishack, Ernest Mui, Shiv K. Verma, and Christopher B. Fox
- Subjects
0301 basic medicine ,biology ,Helper T lymphocyte ,Immunogenicity ,Toxoplasma gondii ,General Medicine ,biology.organism_classification ,Major histocompatibility complex ,Virology ,Epitope ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Immunization ,Antigen ,QR180 ,Immunology ,biology.protein ,030215 immunology - 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.
- Published
- 2016
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