Development of vCJD-Infected Blood Reference Materials

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	FDA/CBER	INFECTDIS-2

Authors

• K.L. McDowell
• N. Nag
• J. Beren
• D.M. Asher
• L. Gregori

Abstract

Transmissible spongiform encephalopathies (TSE) are rare fatal neurodegenerative diseases. Variant Creutzfeldt-Jakob disease (vCJD) is a human TSE important to the FDA because it is transmissible by blood transfusion and plasma products. No test detects vCJD-infected in blood, thus vCJD represents a threat to the safety of the US blood supply. A challenge to developing TSE blood screening tests is the lack of reference materials to validate candidate assays. Because vCJD-infected human blood is not available, we propose to use blood from macaques infected with macaque-adapted vCJD. We infected four macaques with vCJD and are collecting blood monthly. Blood is separated by centrifugation into plasma, buffy coat and red blood cells. In parallel, we infected three mouse strains with macaque brain-derived infectivity to identify the most sensitive model to be used to assay the infectivity in vCJD macaque blood. We have collected 16 samples of vCJD-infected macaque blood spanning 22 months of incubation. Two wild-type mouse lines injected intracerebrally with dilutions of vCJD brain suspension had similar susceptibility to vCJD (infectivity titers ~107 ID50/g of brain). The Tg bovinized mice have been incubating for approximately 300 days; a few Tg mice recently showed typical signs of TSE.

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