RESUMO
Psoralens plus ultraviolet A (UVA) light inactivate viruses and bacteria as well as leukocytes. A system employing the synthetic psoralen compound amotosalen hydrochloride (S-59), in combination with UVA light, is being developed to decontaminate platelet concentrates and plasma in a blood-bank setting. S-59 is a heterocyclic psoralen compound that reacts by a three-step process with nucleic acids (NAs): (1) S-59 intercalates into the double helix; (2) upon illumination with long-wavelength ultraviolet light (UVA), it covalently attaches to a single strand, forming a monoadduct; and (3) additional illumination causes a photoreaction of the monoadduct with the second NA strand, resulting in an interstrand crosslink. The reaction occurs with the genomic material of DNA- and RNA-based viruses and occurs in genomes that are single stranded as well as double stranded. Inactivation rate is related to genome size. Large genomes such as those in leukocytes are far more susceptible to inactivation than are viruses such as hepatitis B virus (HBV), which is inactivated (>10(5) logs) under conditions being developed for blood-bank use. The efficiency of the process is affected by a number of practical considerations such as solution components and light source. The S-59 photochemical treatment process (PCT) has been optimized for platelet concentrates as currently processed for transfusion.
Assuntos
Ficusina/farmacologia , Controle de Infecções/métodos , Leucócitos/efeitos dos fármacos , Transfusão de Plaquetas/normas , DNA/efeitos dos fármacos , DNA/efeitos da radiação , Ficusina/química , Humanos , Leucócitos/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , RNA/efeitos dos fármacos , RNA/efeitos da radiação , Raios UltravioletaRESUMO
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 x 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.