Identification of Problems Developing an Ultrasensitive Immunoassay for the Ante Mortem Detection of the Infectious Isoform of the CWD-Associated Prion Protein

Abstract

Ante-mortem assays exist for some Transmission Spongiform Encephalopathies (TSE). These assays facilitate our understanding of disease pathology and epidemiology; however, the limitations of these ante-mortem assays include the inability to quantify protein amount, poor sensitivity, and/or limited robustness. Here, we utilize a bioinformatics approach to report on problems associated with developing a more sensitive immunoassay for TSEs including: 1) the lack of specific and sufficiently sensitive antibodies for the infectious isoform(s) of PrP^res, 2) problems associated with serial titration of PrP^res, and 3) the distribution of PrP^res particle sizes. Overcoming these problems require more sophisticated antibody design and a creative engineering of an ultrasensitive protein assay systems for PrP^res.

Keywords:

• Bioinformatics study
• Chronic wasting disease
• Immunoassay
• Prion antibodies
• Prion protein
• Ultrasensitive

ACKNOWLEDGMENTS

We would like to acknowledge and thank the Bioinformatics Core Facility in the Center for Rural Health Research and Education (CRHRE) at the University of Wyoming for computing resources and support, especially Storm Knight. This research was funded by the Department of Defense and a US Department of Agriculture CSREES nanotechnology grant.

Manuscript 3322