Effects of lyophilization on the infectivity of enveloped and non-enveloped viruses in bone tissue

Effects of lyophilization on the infectivity of enveloped and non-enveloped viruses in bone tissue
Received 25 February 2005; accepted 15 April 2005. Available online 6 June 2005.
Christine Uhlenhauta, b, Thomas D?rnerb, Georg Paulia and Axel Prussb
Biomaterials
ScienceDirect
aCenter for Biological Safety, Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany
bTissue Bank, Institute for Transfusion Medicine, Charit??University Medicine, Schumannstr. 20/21, 10117 Berlin, Germany
Abstract
Recently reported qualitative experiments proved that retroviral infectivity is not destroyed by lyophilization performed on systemically infected bone and tendon. The now accomplished quantitative determination of residual infectivity for enveloped and non-enveloped viruses allows a validation of the production process regarding viral safety in freeze-dried bone transplants.
The lyophilization effect on the infectivity of two non-enveloped viruses (Maus Elberfeld virus, MEV; Porcine parvovirus, PPV) and one enveloped virus (Vesicular Stomatitis virus, VSV) was examined for virus-spiked bone material in comparison to lyophilized viruses, original virus stock, and air-dried viruses. All experiments were carried out with both cell-free and cell-associated virus. Significant differences were observed regarding the reduction of virus titers (TCID50). Infectivity of VSV was reduced by about 3?4 log10 using lyophilization in presence of bone matrix and of MEV by 6?7 log10, while no substantial reduction in virus titers was observed for PPV. Lyophilization of cell-free or cell-associated virus is not sufficient to inactivate viruses completely. However, lyophilization could have an additive effect in line with other production steps used in the manufacturing process.
Keywords: Bone transplants; Lyophilization; Freeze-drying; Virus safety; Tissue bank
Abbreviations: EMCV, Encephalomyocarditis virus; FeLV, Feline Leukemia virus; HAV, Hepatitis A virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HIV, Human immunodeficiency virus; MEV, Maus Elberfeld virus; moi, Multiplicity of infection; PPV, Porcine parvovirus; TCID50, Tissue culture infectious dose (50%); TSE, Transmissible spongiform encephalopathy; VSV, Vesicular Stomatitis virus

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