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.


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.
Gregori
Luisa
L
Veterans Affairs Maryland Health Care System, VA Medical Center, University of Maryland, Baltimore, Maryland 21201, USA.
Lambert
Brian C
BC
Gurgel
Patrick V
PV
Gheorghiu
Liliana
L
Edwardson
Peter
P
Lathrop
Julia T
JT
Macauley
Claudia
C
Carbonell
Ruben G
RG
Burton
Steven J
SJ
Hammond
David
D
Rohwer
Robert G
RG
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
D008024:Ligands; D011328:Prions