Optimization and evaluation of new decontamination procedures inactivating human prions

[Background] Prions are protein-only infectious agents for which no prophylactic or curative treatment exists. There is a need for formulations effective against human prions and robust in-vitro and in-vivo evaluation protocols.

[Aim] To compare infectivity bioassays with those of their protein misfolding cyclic amplification (PMCA) counterparts to propose a robust method for evaluating prionicide treatments against human prions.

[Methods] Stainless steel wires were contaminated with two humanized prion strains. The wires were then treated with different protocols based on a new formulation termed TFD Premium and World Health Organization (WHO) references. Residual prion seeding activity and infectivity on the wire and in wastewater were quantified using mb-PMCA and ad-hoc bioassays. For vCJD, PMCA compared humanized prions and a human-derived prion isolate.

[Findings] TFD Premium was more efficient at decontaminating humanized prions than 1 N NaOH for 1 h at room temperature. Tg650-sCJD-VV2 was more resistant to inactivation than vCJD prions. For vCJD, strain from both sources showed similar resistant profile against TFD Premium. Finally, there was perfect alignment between the highly sensitive PMCA cell-free assay and the bioassays.

[Conclusion] This study identified a new formulation called TFD Premium, which outperforms or equals the WHO reference methods against human prions and is suitable for manual and automated reprocessing of medical devices in healthcare facilities.

The research reported in this manuscript was supported by FB Product and by grants from the Fondation pour la Recherche Médicale (Equipe FRM DEQ20150331689). The funder FB Product designed and provided the TFD Premium formulation. FB Product participated in the study design, data collection, data analysis, data interpretation, and writing of the report. FRM was not involved in the study design or the writing of the manuscript.

Peer reviewed