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Removal of the Endogenous TSE Infectivity From Blood Using PRDT TSE Affinity Resin And Integration Of The Resin Into The Macopharma P‐CAPT™ Filter
Author(s) -
Rohwer R. G.,
Gregori L.,
Gurgel P. V.,
Lathrop J. T.,
Edwardson P.,
Lambert B.C.,
Carbonell R.G.,
Burton S. J.,
Hammond D. J.
Publication year - 2006
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/j.1365-3148.2006.00694_30.x
Subject(s) - infectivity , hamster , titer , endogeny , scrapie , virology , medicine , whole blood , biology , immunology , pathology , virus , disease , prion protein
Background To date, there have been three transfusion transmitted cases of vCJD among 19 recipients that are known to have received blood from persons that later died of vCJD and lived long enough themselves to have developed detectable disease. This is a transmission rate of ∼15%. A survey of surgically removed tissues concluded that the number of incubating cases of vCJD in the UK was at least 4000. Seven percent of this group would on average be blood donors. Methods Pathogen Removal and Diagnostics Technologies (PRDT) screened millions of compounds to obtain high affinity ligands to prion protein. A group of ligands were challenged with scrapie infected hamster brain homogenate mixed with a unit of leucoreduced human RBC. Infectivity of the challenge and the unbound were compared. To test for removal of the endogenous blood TSE infectivity, blood from scrapie infected hamsters was collected, leucoreduced and passed through the resin. Whole blood, leucoreduced blood and resin flow‐through samples were titered by the limiting dilution method. A total of 5 ml of each sample was inoculated in 50 μl aliquots into 100 hamsters. The experiment was terminated at 540 days and the brain of every animal was checked for evidence of prion amyloid. Results The best resins reduced the titer of the brain‐derived spike into RBC of 10 7 ID 50 /ml by over 4 log 10 ID 50 , far exceeding the capacity needed to capture endogenous RBC infectivity. To address the uncertainty about the relevance of brain‐derived spikes, the lead resin was also assessed for its ability to remove the infectivity endogenously present in blood. There were no infections among the 100 hamsters inoculated with the resin treated blood. The resin removed > 1.2 log 10 ID of relevant TSE blood infectivity. The resin has been incorporated by MacoPharma into the P‐CAPT TM filter, a stand alone device for removing TSE infectivity from leucoreduced red blood cells. Conclusions PRDT's lead resin adsorbs high concentrations (10 7 ID 50 /ml) of brain derived TSE infectivity with high efficiency (4 log 10 ID 50 ) even in the presence of RBC, and removes the low concentrations (10 ID/ml) of endogenous infectivity that is present in leucoreduced whole blood to the limit of detection (>1.2 log 10 ID). Implemented as the Macopharma P‐CAPT TM filter it should significantly reduce the risk of transmission of vCJD by blood and blood products.