title: Effectiveness of a novel immunogenic nanoparticle platform for Toxoplasma peptide vaccine in HLA transgenic mice.
abstract: We created and produced a novel self-assembling nanoparticle platform for delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are protective against Toxoplasma gondii infection. These self-assembling polypeptide nanoparticles (SAPNs) are composed of linear peptide (LP) monomers which contain two coiled-coil oligomerization domains, the dense granule 7 (GRA720-28 LPQFATAAT) peptide and a universal CD4(+)T cell epitope (derived from PADRE). Purified LPs assemble into nanoparticles with icosahedral symmetry, similar to the capsids of small viruses. These particles were evaluated for their efficacy in eliciting IFN-γ by splenocytes of HLA-B*0702 transgenic mice and for their ability to protect against subsequent T. gondii challenge. This work demonstrates the feasibility of using this platform approach with a CD8(+) epitope that binds HLA-B7 and tests the biological activity of potentially protective peptides restricted by human major histocompatibility complex (HLA) class I molecules in HLA transgenic mice.
authors.affiliation: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA. Electronic address: kelbissati@uchicago.edu.
authors.forename: Kamal
authors.initials: K
authors.lastname: El Bissati
authors.affiliation: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
authors.forename: Debleena
authors.initials: D
authors.lastname: Dasgupta
authors.affiliation: George Washington University, 2300 I St. NW Ross Hall, Room 745, Washington, DC 20037, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Cobb
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Building 1001, Beltsville, MD 20705, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: Institute of Materials Science and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Burkhard
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.affiliation: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015793:HLA-B7 Antigen; D007371:Interferon-gamma / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D053758:Nanoparticles / Q000008:administration & dosage*; D010455:Peptides / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000517:prevention & control*; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D010455:Peptides; D016052:Protozoan Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: HLA-B7; Nanoparticles; Toxoplasma gondii; Vaccine
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