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Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma
Author(s) -
Stenland Christopher J.,
Lee Douglas C.,
Brown Paul,
Petteway Stephen R.,
Rubenstein Richard
Publication year - 2002
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.2002.00216.x
Subject(s) - prion protein , prion proteins , human plasma , blood proteins , human proteins , chemistry , virology , biology , biochemistry , medicine , pathology , chromatography , gene , disease
BACKGROUND : Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster‐adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP vCJD ), human sporadic CJD (PrP sCJD ) and Gerstmann‐Sträussler‐Scheinker (PrP GSS ) syndrome was compared to the partitioning of hamster scrapie (PrP Sc ) in three plasma protein purification steps. Sheep scrapie (PrP Sc ) was similarly evaluated. STUDY DESIGN AND METHODS : The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP vCJD , human PrP sCJD , human PrP GSS , sheep PrP Sc , and hamster 263K PrP Sc . The partitioning of the pathogenic form of the PrP was analyzed. RESULTS : Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP Sc . A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (≥3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. CONCLUSIONS : These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.