title: Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies.
abstract: Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue-derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE). Exposed cultures were tested for TSE-associated prion protein (PrP(TSE)) and TSE infectivity by assay in rodents and nonhuman primates. No PrP(TSE) or infectivity has been detected in any exposed cell line under study so far. Animals inoculated with BSE brain homogenate developed typical spongiform encephalopathy. In contrast, animals inoculated with cells exposed to the BSE agent remained asymptomatic. All cell lines we studied resisted infection with 3 TSE agents, including the BSE agent.
authors.affiliation: University of Edinburgh, Easter Bush, UK. pedro.piccardo@fda.hhs.gov
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: Larisa
authors.initials: L
authors.lastname: Cervenakova
authors.forename: Irina
authors.initials: I
authors.lastname: Vasilyeva
authors.forename: Oksana
authors.initials: O
authors.lastname: Yakovleva
authors.forename: Igor
authors.initials: I
authors.lastname: Bacik
authors.forename: Juraj
authors.initials: J
authors.lastname: Cervenak
authors.forename: Carroll
authors.initials: C
authors.lastname: McKenzie
authors.forename: Lubica
authors.initials: L
authors.lastname: Kurillova
authors.forename: Luisa
authors.initials: L
authors.lastname: Gregori
authors.forename: Kitty
authors.initials: K
authors.lastname: Pomeroy
authors.forename: David M
authors.initials: DM
authors.lastname: Asher
mesh_terms: D000818:Animals; D001681:Biological Assay; D016466:CHO Cells; D002417:Cattle; D018929:Cell Culture Techniques; D002460:Cell Line; D002522:Chlorocebus aethiops; D021821:Communicable Diseases, Emerging / Q000635:transmission; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004285:Dogs; D004340:Drug Contamination; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000635:transmission*; D011328:Prions / Q000302:isolation & purification / Q000472:pathogenicity; D012453:Saimiri; D012608:Scrapie / Q000635:transmission; D014612:Vaccines / Q000302:isolation & purification*; D014709:Vero Cells
chemical_list: D011328:Prions; D014612:Vaccines