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Removal of exogenous prion infectivity in leukoreduced red blood cells unit by a specific filter designed for human
Nathalie Lescoutra-Etchegaray1, Chryslain Sumian, Audrey Culeux
1Macopharma, Fontenay-aux-Roses, France.
Background:
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.
Study Design And Methods:
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.
Results:
Incubation periods of recipient animals suggest around a 3-log removal of brain-derived prion infectivity by filtration through the P-Capt.
Conclusion:
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.
Insights
A new P-Capt filter effectively removes prion infectivity from blood, significantly enhancing blood safety for variant Creutzfeldt-Jakob disease (vCJD). This advancement is crucial given the prevalence of silent vCJD infections.
Area of Science:
- Neuroscience
- Transfusion Medicine
- Biotechnology
Background:
- Variant Creutzfeldt-Jakob disease (vCJD) can transmit through blood transfusions from asymptomatic carriers.
- Current safety measures, like leukoreduction, are insufficient to eliminate prion infectivity.
- The prevalence of silent vCJD infections (1/2000 in the UK) necessitates improved blood safety strategies.
Purpose of the Study:
- To assess the efficacy of a novel P-Capt filter in removing prion infectivity from human leukoreduced red blood cells (L-RBCs).
Main Methods:
- The P-Capt filter, integrating affinity resins, was tested on L-RBCs spiked with high levels of hamster brain-derived prion infectivity.
- Hamsters were inoculated with pre- and post-filtration blood samples to evaluate infectivity removal.
Main Results:
- Filtration through the P-Capt filter demonstrated approximately a 3-log reduction in brain-derived prion infectivity.
- The filter's performance was comparable to earlier proof-of-concept studies using affinity resins.
Conclusions:
- The P-Capt filter shows significant potential for efficiently removing prion infectivity from individual human blood bags.
- Implementation of this commercially available filter could substantially improve blood safety against prion diseases like vCJD.
