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

Veterans Affairs Maryland Health Care System, VA Medical Center, University of Maryland at Baltimore, MD 21201, USA.
The Lancet (Impact Factor: 45.22). 01/2007; 368(9554):2226-30. DOI: 10.1016/S0140-6736(06)69897-8
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Available from: Ruben G Carbonell, Aug 01, 2015
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    • "While infection of the lymphoid tissue has no apparent deleterious effects on the health of the affected individual, it is likely to be a significant reservoir of infectivity, which may be spread through blood and blood products. Indeed, infectivity in blood was recently demonstrated in both scrapie-and BSE-infected sheep (Houston et al., 2000, 2008; Hunter et al., 2002) , in deer with CWD (Mathiason et al., 2009), and in rodent models of prion disease (Diringer, 1984; Gregori et al., 2006a,b; Gregori and Rohwer, 2007; Holada et al., 2002; Manuelidis et al., 1978). In addition, blood transfusion or blood products have been implicated in the transmission of vCJD to four human recipients (Hewitt, 2006; HPA, 2007; Llewelyn et al., 2004; Peden et al., 2004; Wroe et al., 2006). "
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    Virology 09/2010; 405(1):110-9. DOI:10.1016/j.virol.2010.05.023 · 3.28 Impact Factor
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    • "The P-CAPT TM Prion Capture Filter is a prion specific filter incorporating prion specific ligands for the selective adsorption of prions in leucodepleted red-cell concentrates (RCC) suspended in additive solution or plasma. It has previously been shown that this technology reduces transmissibility of TSE in blood (Gregori et al., 2006a,b). "
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    • "One has a CE-marked dock-on filter which is used in series with a leucodepletion filter. Published studies using this filter material show >3 log reduction in infectivity on brain homogenate spikes and to the limit of detection (>1 log) in endogenous infectivity studies (Gregori et al, 2006). Two other companies are working on the development of combined leucodepletion/prion reduction filters. "
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    ABSTRACT: There have been four highly probable instances of variant Creutzfeldt-Jakob disease (vCJD) transmission by non-leucocyte depleted red cell concentrates and it is now clear that the infectious agent is transmissible by blood components. To date there in no reported evidence that the infectious agent has been transmitted by fractionated plasma products, e.g. factor VIII concentrate. This review outlines current and potential risk management strategies including donor deferral criteria, the potential for donor screening, blood component processing and prion reduction filters, plasma product manufacture and the difficulties in identification and notification of those considered 'at risk of vCJD for public health purposes'.
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