Design and delivery of a cryptic PrP(C) epitope for induction of PrP(Sc)-specific antibody responses.
Transmissible spongiform encephalopathies (TSEs) depend on misfolding of a normal cellular protein (PrP(C)) to an infectious conformation (PrP(Sc)). Targeting PrP(Sc) may represent an effective strategy for immunotherapy while avoiding consequences associated with immune responses to self-proteins. A weakly immunogenic epitope of PrP(C) (YYR), which induces PrP(Sc)-specific antibodies, is used as a starting point for vaccine development. Through optimization of epitope, as well as formulation/delivery, we enhance immunogenicity while retaining PrP(Sc) specificity. In particular, QVYYRPVDQYSNQN, presented by a leukotoxin carrier protein, emerges as a strong vaccine candidate. A vaccine representing this construct induces consistent and sustained serum PrP(Sc)-specific IgG antibody responses following two vaccinations. Antigen specific antibodies are also present within cerebral spinal fluid and mucosal secretions. These characteristics provide a foundation for development of a TSE vaccine.
Hedlin
Peter D
PD
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatchewan, Canada.
Cashman
Neil R
NR
Li
Li
L
Gupta
Jyotsana
J
Babiuk
Lorne A
LA
Potter
Andrew A
AA
Griebel
Philip
P
Napper
Scott
S
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000097:blood*; D001769:Blood / Q000276:immunology; D002352:Carrier Proteins / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005098:Exotoxins / Q000494:pharmacology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D009092:Mucous Membrane / Q000276:immunology; D018621:PrPC Proteins / Q000235:genetics / Q000276:immunology*; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology* / Q000517:prevention & control*; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000517:prevention & control
D000906:Antibodies; D002352:Carrier Proteins; D000939:Epitopes; D005098:Exotoxins; D007074:Immunoglobulin G; D018621:PrPC Proteins; D018620:PrPSc Proteins; C018579:leukotoxin