title: Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice againstToxoplasma gondii.
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 againstToxoplasma 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-epitope vaccines increased memory CD8+T cells that produced IFN-γ and protected mice against parasite burden when challenged withT.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.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: El Bissati
authors.affiliation: Pathology and Clinical Laboratory Medicine, Department of Immunology, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Aziz A
authors.initials: AA
authors.lastname: Chentoufi
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Paulette A
authors.initials: PA
authors.lastname: Krishack
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Woods
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, Maryland, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: PaxVax Inc., San Diego, California, USA.
authors.forename: Lo
authors.initials: L
authors.lastname: Vang
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lykins
authors.affiliation: Department of Research and Development, Inovio Pharmaceuticals, Blue Bell, Pennsylvania, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Ernest
authors.initials: E
authors.lastname: Mui
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Qila
authors.initials: Q
authors.lastname: Sa
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bi
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Nestor
authors.initials: N
authors.lastname: Cardona
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Beltsville, Maryland, USA.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Verma
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Fraczek
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Reardon
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: PaxVax Inc., San Diego, California, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Alexander
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Vedvick
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Fox
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Guderian
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Reed
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Roberts
authors.affiliation: Department of Opthalmology and Visual Science; and Department of Pediatrics, Infectious Diseases Division (RM), The University of Chicago, Chicago, Illinois, USA.
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000517:prevention & control*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D016052:Protozoan Vaccines