Location: Animal Parasitic Diseases LaboratoryTitle: Adjuvanted multi-epitope vaccines protect HLA-A*1101 transgenic mice against Toxoplasma gondii
|EL BISSATI, KAMAL - University Of Chicago|
|CHENTOUFI, AZIZ - King Fahad Medical City|
|KRISHACK, PAULETTE - University Of Chicago|
|ZHOU, YING - University Of Chicago|
|WOODS, STUART - University Of Strathclyde|
|VANG, LO - Paxvax Inc|
|LYKINS, JOSEPH - University Of Chicago|
|BRODERICK, KATE - Inovio Pharmaceuticals, Inc|
|MUI, ERNEST - University Of Chicago|
|SUZUKI, YASUHIRO - University Of Kentucky|
|BI, STEPHANIE - University Of Chicago|
|CARDONA, NESTOR - University Of Chicago|
|VERMA, SHIV - Non ARS Employee|
|FRAZECK, LAURA - University Of Chicago|
|REARDON, CATHERINE - University Of Chicago|
|SIDNEY, JOHN - La Jolla Institute For Allergy And Immunology|
Submitted to: Journal of Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2018
Publication Date: 9/22/2016
Citation: El Bissati, K., Chentoufi, A., Krishack, P., Zhou, Y., Woods, S., Dubey, J.P., Vang, L., Lykins, J., Broderick, K., Mui, E., Suzuki, Y., Bi, S., Cardona, N., Verma, S.K., Frazeck, L., Reardon, C.A., Sidney, J. 2016. Adjuvanted multi-epitope vaccines protect HLA-A*1101 transgenic mice against Toxoplasma gondii. Journal of Clinical Immunology. http://dx.doi.org/10.1172/jci.insight.85955.
Interpretive Summary: Toxoplasma gondii is a single-celled parasite of all warm-blooded hosts worldwide. It causes mental retardation and loss of vision in children, and abortion in livestock. Cats are the main reservoir of T. gondii because they are the only hosts that can excrete the resistant stage (oocyst) of the parasite in the feces. Humans become infected by eating under cooked meat from infected animals and food and water contaminated with oocyst. Why some people become ill and even die from toxoplasmosis whereas others remain asymptomatic is largely unknown. There is no safe effective vaccine to prevent toxoplasmosis in humans but progress is being made. In the present study authors from APDL, BARC,ARS in collaboration with scientists from several institutions found that vaccination of mice( special mice that have a human gene) with a fraction of protein from Toxoplasma combined with a new adjuvant was protective.These results are encouraging for developing a vaccine and will be of interest to biologists and parasitologists.
Technical 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 five of our best down selected CD8+T cell eliciting epitopes, an universal CD4+ helper T lymphocyte epitope (PADRE), a secretory signal, all arranged for optimal MHC Class I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*1101 transgenic mice. These multi-epitope vaccines increased memory CD8+ T cells that produced IFN-' 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 indicates a novel adjuvanted platform assembly of peptides resulting in cross presentation of CD8+ T cell eliciting epitopes in a vaccine that prevents toxoplasmosis.