title: Blood reference materials from macaques infected with variant Creutzfeldt-Jakob disease agent.
abstract: BACKGROUND
  Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative infection that can be transmitted by blood and blood products from donors in the latent phase of the disease. Currently, there is no validated antemortem vCJD blood screening test. Several blood tests are under development. Any useful test must be validated with disease-relevant blood reference panels.
  
  
  METHODS
  To generate blood reference materials, we infected four cynomolgus macaques with macaque-adapted vCJD brain homogenates. Blood was collected throughout the preclinical and clinical phases of infection. In parallel, equivalent blood was collected from one uninfected macaque. For each blood collection, an aliquot was stored as whole blood and the remainder was separated into components. Aliquots of plasma from terminally ill macaques were assayed for the presence of PrP(TSE) with the protein misfolding cyclic amplification (PMCA) method. Infectivity of the macaque brain homogenate used to infect macaques was titrated in C57BL/6 and RIII J/S inbred wild-type mice.
  
  
  RESULTS
  We sampled blood 19 times from the inoculated monkeys at various stages of the disease over a period of 29 months, generating liters of vCJD-infected macaque blood. vCJD was confirmed in all inoculated macaques. After PMCA, PrP(TSE) was detected in plasma from infected monkeys, but not from uninfected animals. Both mouse models were more sensitive to infection with macaque-adapted vCJD agent than to primary human vCJD agent.
  
  
  CONCLUSIONS
  The macaque vCJD blood panels generated in this study provide a unique resource to support vCJD assay development and to characterize vCJD infectivity in blood.
authors.affiliation: Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: McDowell
authors.forename: Nabanita
authors.initials: N
authors.lastname: Nag
authors.forename: Zulmarie
authors.initials: Z
authors.lastname: Franco
authors.forename: Ming
authors.initials: M
authors.lastname: Bu
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: Juraj
authors.initials: J
authors.lastname: Cervenak
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Deslys
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Comoy
authors.forename: David M
authors.initials: DM
authors.lastname: Asher
authors.forename: Luisa
authors.initials: L
authors.lastname: Gregori
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood* / Q000635:transmission; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011328:Prions / Q000097:blood*; D012015:Reference Standards
chemical_list: D011328:Prions