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Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light
Authors:L Lin  ; DN Cook  ; GP Wiesehahn  ; R Alfonso  ; B Behrman  ; GD Cimino  ; L Corten  ; PB Damonte  ; R Dikeman  ; K Dupuis  ; YM Fang  ; CV Hanson  ; JE Hearst  ; CY Lin  ; HF Londe  ; K Metchette  ; AT Nerio  ; JT Pu  ; AA Reames  ; M Rheinschmidt  ; J Tessman  ; ST Isaacs  ; S Wollowitz  ; L Corash
Institution:Cerus Corporation (formerly Steritech, Inc.), Concord, California 94520, USA.
Abstract:BACKGROUND: A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S- 59, with nucleic acids upon illumination with long-wavelength ultraviolet light (UVA, 320–400 nm). STUDY DESIGN AND METHODS: High levels of pathogens were added to single-donor platelet concentrates containing 3 to 5 × 10(11) platelets in 300 mL of 35-percent autologous plasma and 65-percent platelet additive solution. After treatment with S-59 (150 microM) and UVA (0-3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. RESULTS: The following levels of pathogen inactivation were achieved:>10(6.7) plaque-forming units (PFU) per mL of cell-free human immunodeficiency virus (HIV),>10(6.6) PFU per mL of cell-associated HIV,>10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus),>10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus),>10(6.6) colony-forming units of Staphylococcus epidermidis, and>10(5.6) colony-forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S- 59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. CONCLUSION: Photochemical treatment of platelet concentrates offers the potential for reducing transfusion-related viral and bacterial diseases.
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