Correlation between Bioassay and Protein Misfolding Cyclic Amplification for Variant Creutzfeldt-Jakob Disease Decontamination Studies

• Published in: mSphere Vol. 5; no. 1
• Main Authors: Bélondrade, Maxime, Jas-Duval, Christelle, Nicot, Simon, Bruyère-Ostells, Lilian, Mayran, Charly, Herzog, Laetitia, Reine, Fabienne, Torres, Juan Maria, Fournier-Wirth, Chantal, Béringue, Vincent, Lehmann, Sylvain, Bougard, Daisy
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 26.02.2020
• Subjects: Animals; bioassay; Bioassays; Bovine spongiform encephalopathy; Brain; Cadavers; Caustic soda; Creutzfeldt-Jakob disease; Creutzfeldt-Jakob Syndrome - etiology; Creutzfeldt-Jakob Syndrome - pathology; Decontamination; Decontamination - methods; Dura mater; Equipment Contamination; Female; Growth hormones; Humans; Iatrogenic Disease; Infectivity; Life Sciences; Medical equipment; Mice; Mice, Transgenic; Neurodegenerative diseases; Otolaryngology; Physiology; PMCA; prion; Prion protein; Prion Proteins - chemistry; Prions; Protein folding; Protein seeding; Proteins; Proteostasis Deficiencies - pathology; Sodium; Surgical apparatus & instruments; Therapeutics and Prevention; Transgenic animals; Transgenic mice; variant Creutzfeldt-Jakob disease; Wire; bioassay; prion; variant Creutzfeldt-Jakob disease; decontamination; PMCA
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00649-19

To date, approximately 500 iatrogenic Creutzfeldt-Jakob disease cases have been reported worldwide, most of them resulting from cadaveric dura mater graft and from the administration of prion-contaminated human growth hormone. The unusual resistance of prions to decontamination processes, their large tissue distribution, and the uncertainty about the prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the general population lead to specific recommendations regarding identification of tissue at risk and reprocessing of reusable medical devices, including the use of dedicated treatment for prion inactivation. We previously described an assay, called Surf-PMCA, which allowed us to classify prion decontamination treatments according to their efficacy on vCJD prions by monitoring residual seeding activity (RSA). Here, we used a transgenic mouse line permissive to vCJD prions to study the correlation between the RSA measured and the infectivity. Implantation in mouse brains of prion-contaminated steel wires subjected to different decontamination procedures allows us to demonstrate a good concordance between RSA measured by Surf-PMCA ( ) and residual infectivity ( ). These experiments emphasize the strength of the Surf-PMCA method as a rapid and sensitive assay for the evaluation of prion decontamination procedures and also confirm the lack of efficacy of several marketed reagents on vCJD prion decontamination. Creutzfeldt-Jakob diseases are neurodegenerative disorders for which transmission linked to medical procedures have been reported in hundreds of patients. As prion diseases, they are characterized by an unusual resistance to conventional decontamination processes. Moreover, their large tissue distribution and the ability of prions to attach to many surfaces raised the risk of transmission in health care facilities. It is therefore of major importance that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated for prion inactivation. We previously described an assay, which allowed us to classify accurately prion decontamination treatments according to their efficacy on variant Creutzfeldt-Jakob disease. The significance of this study is in demonstrating the concordance between previous results and infectivity studies in transgenic mice. Furthermore, commercial reagents currently used in hospitals were tested by both protocols, and we observed that most of them were ineffective on human prions.