Susceptibility of cell substrates to PrP^Sc infection and safety control measures related to biological and biotherapeutical products

Abstract

Concerns over the potential for infectious prion proteins to contaminate human biologics and biotherapeutics have been raised from time to time. Transmission of the pathogenic form of prion protein (PrPSc) through veterinary vaccines has been observed, yet no human case through the use of vaccine products has been reported. However, iatrogenic transmissions of PrPSc in humans through blood components, tissues, and growth hormone have been reported. These findings underscore the importance of reliable detection or diagnostic methods to prevent the transmission of prion diseases, given that the number of asymptomatic infected individuals remains unknown, the perceived incubation time for human prion diseases could be decades, and no cure of the diseases has been found yet. A variety of biochemical and molecular methods can selectively concentrate PrPSc to facilitate its detection in tissues and cells. Furthermore, some methods routinely used in the manufacturing process of biological products have been found to be effective in reducing PrPSc from the products. Questions remain unanswered as to the validation criteria of these methods, the minimal infectious dose of the PrPSc required to cause infection and the susceptibility of cells used in gene therapy or the manufacturing process of biological products to PrPSc infections. Here, we discuss some of these challenging issues.

Acknowledgements

The authors would like to thank Monika Tocchi, Dr. Sushama Sontakke and Dr. Mary Alice Hefford for their proofreading and discussion.

Figures and Tables

Table 1 Partial list of cell lines susceptible to PrP^Sc infection

Notes

† The opinions expressed in this paper reflect the authors' personal views, based on published data and the information available from the public domains, and have no relation to the official statements (if any) held by the authors' affiliations.