Vaccine approaches to prevent and treat prion infection : progress and challenges

BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Andreas Müller-Schiffmann, Carsten Korth

Abstract

Prion diseases are transmissible neurodegenerative diseases of humans and animals. The prion agent consists of a misfolded protein, PrPSc (prion protein, scrapie form), of a glycosylphosphatidylinositol-anchored host protein, PrPC (PrP cellular form) of unknown function. During prion replication, PrPSc induces host PrPC to adopt its pathogenic conformation. Some PrPSc may aggregate to microscopically visible, extracellular prion plaques that stain for amyloid. The development of antiprion vaccines presents some challenges. While there is strong self-tolerance to an endogenous antibody response to PrPC and PrPSc, highly potent monoclonal antibodies (mAbs) have been raised in mice in which the prion protein gene has been deleted by gene targeting. These mAbs have been demonstrated to be antiprion-active in permanently scrapie-infected neuroblastoma (ScN2a) cells, primarily when bound to one of four epitopes (the octarepeat region, the region around codons 90-110, helix 1 region codons 145-160, and the extreme C-terminal codons 210-220). The mAbs directed against codon regions 90-110 or 145-160 are also antiprion-active in vivo, but only after intraperitoneal infection with prions, not intracerebral infection, suggesting their blo...Continue Reading

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