title: Methods and Protocols for Developing Prion Vaccines.
abstract: Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.
authors.affiliation: Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E5.|Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E3.
authors.forename: Kristen
authors.initials: K
authors.lastname: Marciniuk
authors.affiliation: Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E5.|Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E3.|School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E5.
authors.forename: Ryan
authors.initials: R
authors.lastname: Taschuk
authors.affiliation: Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E5. scott.napper@usask.ca.|Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada, S7N 5E3. scott.napper@usask.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Napper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D018621:PrPC Proteins / Q000737:chemistry / Q000276:immunology; D017096:Prion Diseases / Q000517:prevention & control*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012449:Safety; D014611:Vaccination; D014612:Vaccines / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology*; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D018621:PrPC Proteins; D014612:Vaccines; D022223:Vaccines, Subunit
keywords: Conformation-specific vaccines; Disease-specific epitopes; Immunotherapy; Prion disease; Proteinopathies; Vaccine