Seminar

Characterization of a Prion distribution and infectivity level in sheep TSE models and evalution of leucodepletion / Prion Trap impact on endogenous infectivity.

Olivier Andreoletti, PhD

The emergence of variant Creutzfeld-Jakob disease and the identification of its potential iatrogenic transmission by blood transfusion and blood components have raised major public health concerns. It led to the implementation of measures intending to prevent Creutzfeld-Jakob disease transmission risk in transfusion medicine. These measures were developed on the basis of limited relevant data on Prion infectivity levels and distribution in blood components. In the present study, using both a natural and an experimental scrapie model in sheep, we established the dynamics of the circulation of the TSE infectivity in blood during incubation phase of the disease. We also evaluated the minimal infectious dose able to transmit disease through blood transfusion and we established the presence of infectivity in plasma, platelets and in different blood mono-nucleated cellular populations. Our finding indicate that 0.2 ml of blood are sufficient to transmit disease and that most of the blood components (including platelets) and mononuclear cell population contain consistent levels of infectivity. We further demonstrated that the fixation of leuco-platelet fraction with paraformaldehyde dramatically impaired their capacity to transmit the disease through transfusion and that extensive washing of the cells had no impact on their infectivity. Finally, using our experimental sheep scrapie model, we investigated the impact of leuco-depletion and of two Prion Trap devices that were proposed to reduce TSE transmission by Red Blood Cell Concentrates (RBCs). Within the limits of our model and of the experiment, our findings strongly support that leuco-depletion is an efficient, whereas not an 100% optimal method to reduce the TSE transmission risk by both RBCs and plasma. It also suggests that Prion Trap might not bring clear beneficial effect (by comparison to leuco-depletion alone) for mitigating the risk of TSE transmission that is associated to the transfusion of RBC.