Removal of exogenous prion infectivity in leukoreduced red blood cells unit by a specific filter designed for human transfusion

Abstract

Five cases of variant Creutzfeldt-Jakob disease (vCJD) infections were attributed to infusion of contaminated blood components, turning to real the interhuman transmissibility of this prion disease from asymptomatic carriers. Preventive policies rely on exclusion from blood donation and benefit of leukoreduction initially implemented against leukotropic viruses. In the absence of available antemortem diagnostic tests, the updated prevalence of silent vCJD infections (1/2000 in the United Kingdom) urges the necessity to enforce blood safety with more efficient active measures able to remove the remaining infectivity. Several affinity resins were demonstrated to reduce high levels of brain-spiked infectivity from human leukoreduced red blood cells (L-RBCs). One was integrated in a device adapted to field constraints (volumes, duration) of human transfusion. We assessed here the ability of the resulting removal filter, termed P-Capt, to remove infectivity from human L-RBC units spiked with scrapie-infected hamster brain (≥10,000 infectious units/mL), through inoculation of hamsters with pre- and post-blood filtration samples. Incubation periods of recipient animals suggest around a 3-log removal of brain-derived prion infectivity by filtration through the P-Capt. On brain-derived spiked infectivity, the P-Capt filter provided a performance similar to the resin packed in columns used for initial proof-of-concept studies, suggesting an appropriate scale-up to efficiently remove infectivity from an individual human blood bag. According to the ability of resin to completely remove apparent endogenous infectivity from hamster leukoreduced blood, the implementation of such a filter, now commercially available, might seriously improve blood safety toward prions.