Steven James Burton

Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins

BACKGROUND Transmissible spongiform encephalopathies (TSE) can be contracted through blood transfusion. Selective adsorption of the causative agent from donated blood might be one of the best ways of managing this risk. In our study, affinity resin L13, which reduces brain-derived infectivity spiked into human red blood cell concentrate by around 4 log(10)ID(50), and its equivalent, L13A, produced on a manufacturing scale, were assessed for their ability to remove TSE infectivity endogenously present in blood. METHODS 500 mL of scrapie-infected hamster whole blood was leucoreduced at full scale before passage through the affinity resins. Infectivity of whole blood, leucoreduced whole blood (challenge), and the recovered blood from each flow-through was measured by limiting dilution titration. FINDINGS Leucoreduction removed 72% of input infectivity. 15 of 99 animals were infected by the challenge, whereas none of the 96 or 100 animals inoculated with the final flow-throughs from either resin developed the disease after 540 days. The limit of detection of the bioassay was 0.2 infectious doses per mL. The overall reduction of the challenge infectivity was more than 1.22 log10ID. The results showed removal of endogenous TSE infectivity from leucoreduced whole blood by affinity ligands. The same resins adsorb normal and abnormal prion protein from human infections with variant, sporadic, and familial Creutzfeldt-Jakob disease, in the presence of blood components. INTERPRETATION TSE affinity ligands, when incorporated into appropriate devices, can be used to mitigate the risks from TSE-infected blood, blood products, and other materials exposed to TSE infectivity.

Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands

BACKGROUND:  There is a demonstrated risk of infection by transmissible spongiform encephalopathies (TSEs) through transfusion from asymptomatic donors. Currently, blood‐borne TSE infectivity cannot be detected with a diagnostic test, nor is it likely to be amenable to inactivation; however, its depletion with specific adsorp‐tive ligand resins is possible.