title: Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands.
abstract: 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.
  
  
  METHODS
  Six ligands that bind the prion protein, PrP, were selected by screening large solid-phase combinatorial chemical libraries. The selected resins were placed in columns and challenged with a unit of leukoreduced human red blood cells (RBCs) spiked with hamster brain-derived scrapie infectivity. The performance of each ligand was assessed by comparing the TSE infectivity titer in the RBCs before and after passage through each of five resin columns in series.
  
  
  RESULTS
  Four resins were able to reduce infectivity titer by 3 to more than 4 log ID(50) per mL. The reduction was not due to nonspecific matrix interactions since a chemical modification of the most effective ligand completely abolished its ability to bind infectivity (negative control). A small subfraction of the infectivity, 0.01 percent, could not be removed, even upon repeated passage through successive columns.
  
  
  CONCLUSIONS
  If endogenous TSE infectivity in RBCs binds to the ligands in the same proportion as brain-derived infectivity spiked into RBCs, the four most effective ligands would remove 3 to 4 log ID(50) per mL. A follow-up experiment is in progress to test whether endogenous blood-borne infectivity is also reduced.
authors.affiliation: Veterans Affairs Maryland Health Care System, VA Medical Center, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Gregori
authors.forename: Brian C
authors.initials: BC
authors.lastname: Lambert
authors.forename: Patrick V
authors.initials: PV
authors.lastname: Gurgel
authors.forename: Liliana
authors.initials: L
authors.lastname: Gheorghiu
authors.forename: Peter
authors.initials: P
authors.lastname: Edwardson
authors.forename: Julia T
authors.initials: JT
authors.lastname: Lathrop
authors.forename: Claudia
authors.initials: C
authors.lastname: Macauley
authors.forename: Ruben G
authors.initials: RG
authors.lastname: Carbonell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burton
authors.forename: David
authors.initials: D
authors.lastname: Hammond
authors.forename: Robert G
authors.initials: RG
authors.lastname: Rohwer
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D017707:Erythrocyte Transfusion / Q000379:methods / Q000592:standards; D004912:Erythrocytes / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D017096:Prion Diseases / Q000517:prevention & control*; D011328:Prions / Q000097:blood / Q000302:isolation & purification*; D011485:Protein Binding; D017186:Titrimetry
chemical_list: D008024:Ligands; D011328:Prions