PHOTOINACTIVATION OF VIRUSES IN PLATELET SUSPENSIONS

血小板悬浮液中病毒的光灭活

• 批准号: 3358871
• 负责人: Roger Y. Dodd
• 金额: $ 20.97万
• 依托单位: AMERICAN NATIONAL RED CROSS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358871
• 关键词: Sindbis virus; Vesiculovirus; antiseptic sterilization; blood banks; encephalomyocarditis virus; human immunodeficiency virus 1; human tissue; light adverse effect; plaque assay; platelets; psoralens; radiation dosage; radiosensitizer; suid alphaherpesvirus 1; ultraviolet radiation

Transmission of infection is the most frequent and serious negative outcome of blood transfusion, despite extensive donor screening and laboratory testing. It is estimated that up to 100 recipients of blood and its components may be infected with HIV in the United States each year and prospective studies have been interpreted to suggest that up to 300,000 recipients may be infected have hepatitis viruses that have a potential for causing serious or lethal long term sequelae. Herpes viruses continue to be a problem for immunocompromised recipients and newly recognized retroviruses are generating concern. Among recipients of blood components, approximately 250,000 patients receive platelet concentrates annually; most of these recipients are under treatment protocols which result in profound immunosuppression. The nature of platelet concentrates does not permit simple physical methods of removing infectious contaminants. Certain photoinactivation procedures are specific for nucleic acids; preliminary investigations suggest that conditions which inactivate 5-6 logs of model viruses do not interfere with platelet function. Safe, effective photoinactivation protocols will be developed to inactivate 6 logs of HIV in both plasma and cellular compartments in platelet concentrates. These methods will be evaluated and modified as appropriate to eliminate 5-6 logs of more resistant model viruses. Screening methods will be used to assess the separate effects of photoinactivators and long-wave UV on viruses and platelets in controlled conditions. Conditions which inactivate 6 logs of virus but retain platelet morphology will be investigated in more depth in a platelet concentrate environment to assess mechanisms of platelet damage and to understand the kinetics and mechanism of nucleic acid damage in this milieu. Toxicologic studies will be carried out so that delivery methods, can, if necessary, be designed to incorporate means to remove added chemicals.

感染的传播是最频繁和最严重的 尽管有大量的供体，但输血的阴性结局 筛查和实验室检测。 据估计，多达100 血液及其成分的接受者可能感染艾滋病毒 在美国每年和前瞻性研究已经 这意味着多达300，000名接受者可能会被 感染了肝炎病毒，有可能导致 严重或致命的长期后遗症。 疱疹病毒继续 对于免疫功能低下的接受者和新的 公认的逆转录病毒正在引起关注。 之间 血液成分接受者，约25万名患者 每年接受血小板浓缩物;这些接受者中的大多数 正在接受治疗， 免疫抑制 血小板浓缩物的性质不 允许简单的物理方法去除传染性 污染物。 某些光灭活程序是特定的 对于核酸;初步调查表明， 15 -6个对数的模型病毒不具备的条件 干扰血小板功能。 安全有效 光灭活方案将发展到106个log 在血小板的血浆和细胞区室中的HIV 浓缩物。 这些方法将被评估和修改， 适合于消除5-6个对数的更具抗性的模型病毒。 筛选方法将用于评估以下因素的单独影响： 光灭活剂和长波紫外线对病毒和血小板的作用 控制条件。 病毒感染量超过6个日志的条件 但保留血小板形态将进行更深入的研究 在血小板浓缩物环境中， 血小板损伤和了解动力学和机制， 在这种环境下的核酸损伤。 毒理学研究将 执行，以便交付方法，如有必要， 设计成结合去除添加的化学物质的装置。