Optimization and evaluation of new decontamination procedures inactivating human prions.

Abstract

Background: Prions are protein-only infectious agents for which no prophylactic or curative treatment exists. Infectivity bioassays based on hamster-263K prions allowed to identify processes capable of inactivating prions on medical devices. However, a 2016 publication study revealed that detergent formulations effective against hamster strain had poor efficacy against human strains. Shortly after, three probable cases of accidental Creutzfeldt-Jakob disease underscored the risk for scientists, health workers, and patients exposed to contaminated materials. The governmental guidelines were modified and emphasizing the need for formulations effective against human prions and robust in vitro and in vivo evaluation protocols. Here, we aimed to compare infectivity bioassays with those of their 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 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 proved more efficient at decontaminating humanized prions than 1 N NaOH for 1 hour at room temperature. Tg650-sCJD-VV2 were more resistant to inactivation than vCJD prions. For vCJD, strain from both sources shown similar resistant profile against TFD Premium. Finally, there was perfect alignment between the highly sensitive PMCA cell-free assay and the bioassays.