Variant Creutzfeldt-Jakob Disease (vCJD)
Introduction
vCJD is one of the human forms of Transmissible Spongiform Encephalopathies (TSEs). The disease was first identified in 1996. It is generally believed that vCJD is caused by the consumption of BSE infected products. Symptoms of this fatal brain disease include depression, involuntary muscle contractions and impaired muscular co-ordination. In contrast to typical cases of classical CJD, vCJD seems to affect predominantly young patients. As of 2007, over 180 cases of vCJD have been reported worldwide; most of which are in the United Kingdom (UK). The first ten cases of vCJD were observed in 1996, approximately ten years after the outbreak of the BSE epidemic in the UK.
Human Health Risk
The primary risk of humans developing the new form of variant Creutzfeldt-Jakob Disease (vCJD) is through eating BSE-contaminated food products. Moreover, transmission from humans to humans (iatrogenic transmission) can occur via contaminated surgical equipment, tissue transplantations as well as through blood or blood products.
The presence of prion infectivity in blood or in blood constituents during both the incubation period and the clinical phase of the disease have been reported in several studies of experimental animal models of Transmissible Spongiform Encephalopathies (TSE).
As of 2007, four likely vCJD transmissions via blood transfusion have been reported in the UK.
Typically, vCJD-infected individuals are asymptomatic for prolonged times, despite infectivity in their blood. This raises the risk for donations of contaminated blood and the subsequent transmission of the disease. Detailed investigations into one of the above cases has documented that infectivity may be sufficient for transmission as early as three years prior to disease onset in the donating individual itself.
Despite the urgent need, there is no diagnostic test currently available that can detect this disease in blood.
Impact
An infected blood donor can potentially infect a large group of recipients, accelerating the spread of the disease. The rate of infection may be enhanced by long incubation times and a high number of infected people.
Precautionary measures to prevent such transmissions vary from country to country and include deferral of blood donors who have lived for extensive periods in certain European countries (see for example the FDA Guidelines for Industry).
As a protective measure against any risk from blood transfusions, in the UK blood must be leucodepleted before transfusion; i.e., white cells, which experts believe represent the main risk of vCJD infection, are removed.
The inability to effectively and efficiently detect the presence of vCJD in blood has resulted in a shortage of human blood supplies as well as enormous additional costs for human blood banks. Moreover the social aspect of recipients of potentially infected blood donations should not be neglected.
Diagnostic solution
A key focus of the Prionics R&D team is the development of a live test for the detection of prion disease in human blood. In order to prevent a potential spread of vCJD through blood donations or blood products, there is a need for a live prion test for use in the human blood sector. To this end Prionics is developing a blood test for the specific detection of the disease causing prion protein in blood.
Concentrations of the disease-specific form of the prion protein (PrPvCJD) are several orders of magnitude lower than those in brain tissues and hence, enrichment of PrPvCJD is required to detect PrPvCJD in body fluid samples.
Prionics proprietary monoclonal antibody 15B3 specifically recognizes the disease-associated form of the prion protein and is capable of detecting PrPvCJD in brain homogenates without the need for Proteinase K digestion. This is of considerable importance for its application in blood, as it has been shown that prion infectivity in blood is sensitive to protease digestion and therefore might not be detected in methods using protease digestion.
15B3 is an IgM isotype antibody that can be used as a capture antibody in sandwich ELISAs or in immunoprecipitation experiments followed by detection using Western blotting, FACS analysis or the eQuIC procedure (Orrú et al., 2011).
