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.
Highlights
Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue–derived medical products, human blood components, and animal vaccines
We investigated the susceptibility of cell lines used or proposed for manufacture of biologics and controls to propagate TSE agents, especially the bovine spongiform encephalopathy (BSE) agent, under simulated worst-case conditions
Mice inoculated with the bacteria-free filtrate of 1% BSE-infected brain suspension used to expose cells developed signs of TSE, and PrPTSE was detected in brains, demonstrating that the inoculum used to expose cell cultures contained a TSE agent transmissible to mice (Figure 1)
Summary
Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue–derived medical products, human blood components, and animal vaccines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE). Many investigators once believed that TSE agents infected mainly, if not exclusively, cells of neuronal and lymphoid lineages. The theoretical risk of contaminating vaccines or other biologic products prepared in culture cells with TSE agents from animal-derived materials in media has been considered low. 1) as noted above, the blood of asymptomatic humans has transmitted vCJD, and 2) in a variety of experimentally TSE-infected animals, TSE agent has been detected in blood, mainly in nucleated cells and plasma [4,5,6,14,15,16,17].
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