Figures & data
Figure 1. Effects of PrPC immunotherapy on reducing amplification of PrPSc.
Figure 2. Effect of conformation-specific immunotherapy on endogenous PrPC and PrPSc.
Figure 3. Mapping of PrPSc DSEs. Location of YML (green), YYR (orange), and RL (red) disease-specific epitopes within tertiary and primary structure of PrP. Adapted from James et al.Citation50
Figure 4. Immunogenicity of YYR vaccines in sheep. YYR epitope vaccines were generated as C-terminal fusions to the carrier protein leukotoxin. Epitopes were generated through N and C-terminal expansion of the YYR core, using the PrP protein sequence. In the recombinant protein, epitopes were presented in a repeat motif in either a linear (L) or inverted (I) presentation. Median titers represent serum antibody titers two weeks after a boost immunization.
Figure 5. Specificity and safety of conformation-specific immunotherapy. (A) Sheep (n = 7) received the β2(2+YYR+9)I vaccine at 6-wk intervals. Pre-immune and immune serum from high titer animals were evaluated for the ability to bind PrPC via ELISA. (B) Sheep were immunized three times at 6-wk intervals with the either of the various YYR-based vaccines noted. Immune sera conjugated to magnetic beads were used in immunoprecipitation experiments with brain homogenates from uninfected (wt) and scrapie-infected mice (RML). (C) Polyclonal β2(2 + YYR + 9)I coupled to beads was used in immunoprecipitation experiments with lysates from HEK293T cells expressing either wt PrPC or the T194A PrPC mutant. (D) PK digests and western blots of combined brain and spleen homogenates from six β2(2 + YYR + 9)I-vaccinated / aged or infected tga20 mice.
Figure 6. Active immunization and oral challenge of sheep. Pregnant ewes (n = 2/group) received two immunizations of either Lkt or Lkt-β2(2+YYR+9)I vaccine at six and three weeks prior to birthing. Lambs born from Lkt (n = 4) or Lkt-β2(2 + YYR + 9)I (n = 3) vaccinated ewes were challenged with 1 g of scrapie brain homogenate via gastric feeding immediately following birth. Animals were continuously monitored for the onset of scrapie symptoms by 24 h video surveillance.
