An Immunoprotectant for Marburg Virus

描述(由申请人提供)：与马尔堡病毒(Marv)暴发有关的死亡率从23%到90%以上不等。MARV被美国疾病控制和预防中心列为A类药物，即“对国家安全构成风险的高优先级药物。”MARV不仅会引起死亡率高的急性可怕疾病，而且在潮湿或干燥的气雾剂中相对稳定；它具有高度传染性(LD50约为1个空斑形成单位，或PFU)，无论是通过肠道外还是通过气溶胶感染；它可以在细胞培养物或动物中生长到极高的滴度；它容易被医院和医源性传播给卫生保健人员，并由卫生保健人员传播；作为一种非洲地方性病毒，它可能由足智多谋的个人或群体通过反复自然暴发感染。目前还没有预防或治疗Marv感染的药物。显然，对MARV免疫保护剂的需求尚未得到满足，以解决生物武器以及由定期自然发生的疫情引起的公共卫生问题。用抗体进行被动免疫已被证明对影响人类的各种病毒、细菌、真菌和寄生虫病有效。这项由MAPP生物制药公司和美国陆军传染病医学研究所合作的建议的产品开发目标是：(1)产生一组全人抗MARV单抗；(2)根据在小鼠模型中的疗效选择主要抗MARV单抗；以及(3)比较在哺乳动物细胞培养中表达的主要单抗与在快速、低成本、高度可扩展的生产系统中表达的相同单抗的保护效力。除了节省成本外，该系统还提供了快速反应制造能力，可用于解决其他生物防御以及新出现和重新出现的传染病病原体。该项目的长期目标是开发一种安全有效的Marv免疫保护剂产品。与公共卫生相关：这项提案中的努力将有助于开发一种预防和/或治疗马尔堡病毒的药物，马尔堡病毒是一种潜在的生物制剂，目前尚无治疗方法。

DESCRIPTION (provided by applicant): Mortality rates associated with Marburg virus (MARV) outbreaks range from 23% to over 90%. MARV is included by the Centers for Disease Control and Prevention as among the Category A agents, or "high-priority agents ... that pose a risk to national security." MARV not only causes acute and terrifying disease with high mortality rates, but it is relatively stable in wet or dry aerosols; it is highly infectious (LD50 is approximately 1 plaque-forming unit, or PFU) whether infection occurs parenterally or by aerosol; it can be grown to exceedingly high titers in cell cultures or animals; it is subject to nosocomial and iatrogenic spread to and by health care personnel; and as an endemic African virus it could be acquired from recurrent natural outbreaks by a resourceful individual or group. There are currently no drugs available for preventing or treating infections with MARV. There is a clear unmet need for a MARV immunoprotectant to address biowarfare as well as public health concerns raised by regular naturally occurring outbreaks. Passive immunization with antibodies has been shown to be effective against a wide variety of viral, bacterial, fungal, and parasitic diseases that affect humans. The Product Development Goals of this proposal - a collaboration between Mapp Biopharmaceutical and the U.S. Army Medical Research Institute of Infectious Diseases - are to: (1) generate a panel of fully human anti-MARV Mabs; (2) select lead anti-MARV Mabs based upon efficacy in mouse models; and (3) compare the protective efficacy of the lead Mabs when expressed in mammalian cell culture with the identical Mabs expressed in a rapid, low-cost, highly scalable manufacturing system. In addition to the cost savings, this system offers a rapid response manufacturing capability that can be used to address other biodefense and emerging and re-emerging infectious disease pathogens. The Long Range Objective of this project is to develop a safe and effective immunoprotectant product for MARV. PUBLIC HEALTH RELEVANCE: The efforts in this proposal will help in the development of a drug for preventing and/or treating Marburg virus, a potential biowarfare agent, for which no treatment currently exists.