NR AORW
AU Dickinson,J.; McLeod,A.H.; Hall,G.A.; Dennis,M.J.; Murdoch,H.; Sutton,J.M.; Raven,N.D.H.
TI Novel methods for the proteolytic inactivation of TSEs; correlation between loss of specific immunoreactive material and infectivity
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-18
PT Konferenz-Poster
AB
The potential for iatrogenic spread of Creutzfeldt-Jakob disease (CJD) during routine surgery has been well described in clinical cases and animal models. The emergence of a variant form of the disease (vCJD) presenting in young patients has increased the likelihood of transmission via this route. The exceptional stability of the agent to standard methods of inactivation poses unique problems for the decontamination of surgical instruments.
We report here a novel method for the proteolytic inactivation of prion proteins designed for use in the decontamination of surgical instruments. Thermostable proteases at defined temperature and pH have the ability to rapidly degrade prion proteins. Using a BSE(301V) VM mouse model of prion disease we have demonstrated that the removal of all immunoreactive material, recognised by the commercial anti-prion antibody 6H4, results in a significant but incomplete reduction in infectivity. Using our own antibody reagents we have identified a series of protease resistant prion molecules of 40-70kDa. We propose that these may be novel isoforms of the prion protein and are responsible for the residual levels of infectivity. Their elimination results in a greater than 5-log reduction in infectious dose with many mice surviving to old age. These results will be discussed in relation to the development of methods of prion inactivation.
AD J. Dickinson, A.H. McLeod, G.A. Hall, M.J. Dennis, H. Murdoch, J.M. Sutton, N.H.D. Raven, HPA - Porton Down, UK
SP englisch
PO Deutschland