Publications and News

Recent Publications

bioRxiv

bioRxiv

Prion shedding is reduced by chronic wasting disease vaccination

Hanaa Ahmed Hassan, Dalia Abdelaziz, Yo-Ching Cheng, Kevin Low, Shirley Phan, Byron Kruger, Chimone Dalton, Lech Kaczmarczyk, Walker Jackson, Sabine Gilch, Hermann Schatzl‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30-90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle. (Currently in review with PLOS | Pathogens)

See More
Scientific reports

Nature Portfolio | Scientific reports

PLGA nanoparticles for oral delivery of prion-specific antigen: a novel approach

Mohamed M. Elsutohy, Dalia Abdelaziz, Chimoné S. Dalton, Byron Kruger, Shirley Phan, Yo-Ching Cheng, Kevin Low, Hanaa Ahmed-Hassan & Hermann M. Schätzl ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Prion diseases, such as chronic wasting disease (CWD), are incurable, fatal neurodegenerative disorders. We have developed a recombinant dimeric deer prion protein (Ddi) vaccine against CWD that has shown promising immune responses when injected subcutaneously (s.c). While s.c injection is suitable for controlled conditions, oral administration is practical in wildlife. Herein, we have developed an oral vaccine utilizing poly lactic co-glycolic acid (PLGA) nanoparticles, co-encapsulating Ddi and oligodeoxynucleotide adjuvant (CpG) using double emulsion-solvent evaporation technique. Our results showed production of spherical PLGA nanoparticles with size of ~ 200–300 nm, an acceptable surface charge (− 14.2 ± 5.73 mV), and an encapsulation efficiency of approximately 70 and 30%, for Ddi and CpG, respectively. We administered the developed vaccine to FVB mice orally and subcutaneously, followed by ELISA assays of the sera and feces. Mice receiving the vaccine subcutaneously exhibited high antibody reactivities to the used antigen in their sera (100% positivity), with no detectable positive reactivity in their feces. However, those receiving the oral vaccine showed 60 and 80% positivity in sera and feces, respectively, indicating specific mucosal immunity. We also found specific T cell reactivity in mice immunized orally. This approach is paving the way for developing an oral vaccine against CWD.

See More
Autophagy

Taylor and Francis | Autophagy

Contrasting roles of autophagy in cellular prion infection

Basant Abdulrahman, Andreas Heiseke, Yasmine Aguib, Li Lu, Dalia Abdelaziz, Mariam Ansari, Simrika Thapa, Yuzuru Taguchi, Sabine Gilch, and Hermann M. Schätzl ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ ‎ Autophagy is a cellular degradation program that can exert both beneficial and adverse effects invarious neurodegenerative diseases. We tested the role of macroautophagy/autophagy in prioninfection and how this machinery affects the life cycle of prions. In mouse embryonic fibroblasts,we found a pronounced dependence of prion replication on autophagy competence, suggesting thatautophagy provides functions needed for prion propagation. However, in neuronal cells, autophagyhad mostly the opposite role. Cells ablated for autophagy competence by gene editing harboredelevated amounts of misfolded prion protein, indicating that neuronal cells use autophagy for priondegradation. These data show that autophagy can have two functions in the replication of prions,and depending on the cellular context, this can be protective against or supportive of prion infection.These findings demonstrate that prions use cellular machineries to benefit propagation in certain celltypes, whereas other cell types employ the same machinery as a defense mechanism

See More

More Publications From the Schaetzl Lab

In the News

  1. UCalgary News

    UCalgary researchers at work on a vaccine against a fatal infectious disease affecting deer and potentially people

     

    Read More

  2. CBC News | Edmonton

    Chronic wasting disease threatens deer, elk — and maybe humans, new research says ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  

     

    Read More

  3. CTV News | Calgary

    Alberta uses hunters to reduce deer numbers in effort to slow spread of debilitating disease‎ ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

    Read More

  4. The Western Producer

    CWD may have ability to jump to humans ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

    Read More

  5. Bovine Veterinarian

    University of Calgary Vaccine Protects Against CWD ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎  ‎ ‎ ‎ ‎ ‎ 

     

    Read More