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2011 Call for projects in the field of viral safety for biological products
  » Outcome

Selected projects 2009

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Assessment of prion infectivity in blood in primate and sheep models,
and evaluation of removal processes

PI : D. Dernis - Etablissement Français du Sang Nord, Lille - France 
Other Investigators : E. Comoy - Commissariat à l’Energie Atomique, DSV/IMETI/SEPIA,      Fontenay-aux-Roses - France
H. Laude - INRA , Jouy en Josas - France
B. Flan - LFB, Les Ulis - France
J.Coste - EFS Pyrénées-Méditerranée, Montpellier - France

Blood is infectious in some prion diseases, presumably including the variant of Creutzfeldt-Jakob disease that is linked to the transmission of Bovine Spongiform Encephalopathy agent to human. Indeed, four patients are supposed to have been contaminated through transfusion with labile blood products (non deleucocyted red cell fractions) issued from vCJD-affected donors. More recently, a hemophiliac patient demonstrated peripheral replication of PrPres while he received coagulation factors issued from a vCJD-infected donor. Experimental models suggest that blood infectivity would be mainly supported by white cells, but other blood components could also be infectious.

 The project “PrionBloodPrimate” has been set up to refine the risk assessment of prion for blood products, through the analysis of prion infectivity distribution among the different blood components, and to evaluate the ability of different methods to remove prion infectivity during blood processing. These studies are based on both primate and sheep experimental models, to associate the benefits of each of them: on one hand, primates (cynomolgus macaques) have been demonstrated as a very relevant model of ‘natural’ human contaminations modeling the different potent scenarios of vCJD transmission (primary oral or secondary intravenous contaminations), but amounts of recovered blood are limited. On the other hand, scrapie experimentally infected sheep have different prion strains but they provide amounts of blood similar to those obtained from human, allowing to test the standard volumes with the fractionation techniques from blood donation.

Blood samples are first fractionated in cellular (buffy coat and red cell concentrates) and acellular (plasma) components. On one hand, the different cell populations are separated with the Foundation’s secured cell sorter; on the other hand, the widely used first steps of plasma fractionation (Cohn fractionation, cryoprecipitation, ethanol concentration…) are applied on plasma.

Infectivity of the different subfractions is assessed through in vitro (PMCA, infectable cell cultures) and in vivo approaches (bioassay in original, rapid and sensitive models of humanized and ovine transgenic mice for primate and sheep models respectively). Since low level of infectivity is attended, some samples will be submitted to PMCA amplification prior to infectivity assessment.
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