Prion Blood Primate
Assessment of prion infectivity in blood in primate and sheep models, and evaluation of removal processes
- P.I. Dominique Dernis, Etablissement Français du Sang (EFS -Nord de France), Lille, France
- Emmanuel Comoy, Commissariat à l’Energie Atomique – DSV/IMETI/SEPIA, Fontenay-aux-Roses, France
- Hubert Laude, Institut National de la Recherche Agronomique (INRA), Jouy en Josas, France
- Benoît Flan, LFB, Les Ulis, France
- Joliette Coste, EFS - Pyrénées-Méditerranée, Montpellier, France
- Karel Holada , Institute of Immunology and Microbiology, 1stFaculty of Medicine Charles University in Prague, Prague, Czech Republic
2007: 3 years / Grant: 206 000 euros
Project: The aims of the project were 1) to assessthe risk of prion blood contamination through the
use of non human primates infected with vCJD or BSE, and 2) to evaluate the risk of prion content
in blood samples and blood derivatives after treatments designed to reduce plasmatic protein levels
applied in transfusion centers.
Results and related published data: The work of different collaborating laboratories was not
finished at the time of the final report, as some primate prion infection steps required a couple of
years to be completed. During this project, and due in part to the financial support of Alliance
Biosecure, the use of the Tg650 HuPrP transgenic mice forvCJD transmission (from brain tissue first)
was validated. The possibility to detect PrPTSE in the spleen long before its detection in the brain
was also described, and was shown to be as sensitive as animal survival time bioassay. For the
second part of this project, the detection of PrPTSE in blood cells from primate infected with vCJD
was performed. Infectivityin primate blood samples was evidenced through bioassayin conventional
mice but not in Tg650 Hu PrP transgenic mice. In an independent project, those samples were also
found positive through PrPTSE PMCA amplification (with this technique, detection in blood, white
blood cells or buffy coat from non-human primate vCJD experimental models, was obtained even
during the early preclinical stage of the incubation period). In addition, while developing protocols
to detect PrPTSE in blood cells, the consortium reported the fact that blood storage might affect the
detection of PrPC and potentially a non-specific binding of “PrPTSE antibody”.
- Analysis of PrPC/PrPTSE expression on monocytes and circulating dendritic cells of
healthy and TSE infected cynomolgus macaques (Macaca fascicularis). Janouskova O,
Vranac T, Glierova H, Comoy E, Curin-Serbec V, Deslys J.P, Holada K., poster P.2.14, Prion 2009, Porto
- Binding of prion antibodies to white blood cells of nonhuman primates and the existence
of washable pool of cellular prion protein associated with lymphocytes in peripheral
blood. Holada K, Glierova H, Janouskova O. Transfusion. 2010 Sep;50(9):2063-5; author reply 2065-
6. doi: 10.1111/j.1537-2995.2010.02707.
- Facilitated cross-species transmission of prions in extraneural tissue. Béringue V, Herzog
L, Jaumain E, Reine F, Sibille P, Le Dur A, Vilotte JL, Laude H. Science. 2012 Jan 27;335(6067):472-
5. doi: 10.1126/science.1215659.
- Blood storage affects detection of cellular prion proteinon lynphocyte subpopulation and
on circulating dendritic cells, Glierova H, Holada K, Journal of Immunological Methods [2012,
- Accelerated, spleen-based titration of variant Creutzfeldt-Jakob disease infectivity in
transgenic mice expressing human prion protein with sensitivity comparable to that of
survival time bioassay. Halliez S, Reine F, Herzog L, Jaumain E, Haïk S, Rezaei H, Vilotte JL,Laude
H, Béringue V. J Virol. 2014 Aug;88(15):8678-86. doi: 10.1128/JVI.01118-14. Epub 2014 May 21.
- Preclinical detection of variant CJD and BSE prions in blood. Lacroux C, Comoy E, Moudjou
M, Perret-Liaudet A,Lugan S,Litaise C, Simmons H, Jas-Duval C,Lantier I, Béringue V, Groschup M,
Fichet G, Costes P, Streichenbergr N,LantierF, Deslys JP, Vilette D, Andréoletti O. PLoS Pathog. 2014
Jun 12;10(6):e1004202. doi: 10.1371/journal.ppat.1004202. eCollection 2014.