Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads

Simone HornemannID1 *, Petra Schwarz1 , Elisabeth J. Rushing1 , Michael D. Connolly3 , Ronald N. Zuckermann3 , Alice Y. Yam2¤ , Adriano AguzziID1 * 1 Institute of Neuropathology, University of Zurich, Zurich, Switzerland, 2 Novartis Vaccines and Diagnostics Inc., Emeryville, California, United States of America, 3 Biological Nanostructures Facility, The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America ¤ Current address: Sutro Biopharma, San Francisco, California, United States of America * (AA); (SH)


Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoidbased misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.


Docket Number: FDA-2012-D-0307 Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry Singeltary Submission