An Immunoprotectant for Marburg Virus

描述（由申请人提供）：马尔堡病毒（MARV）暴发相关的死亡率从23%到90%以上不等。MARV被疾病控制和预防中心列为A类药剂，或“高优先级药剂”。这对国家安全构成了威胁。”MARV不仅引起急性可怕的疾病，死亡率高，而且在湿或干气溶胶中相对稳定；无论是通过肠道感染还是通过气溶胶感染，它都具有高度传染性（LD50约为1个斑块形成单位，简称PFU）；它可以在细胞培养物或动物中培养到非常高的滴度；它受到医院和医源性传播的影响，并由卫生保健人员传播；作为一种非洲地方性病毒，它可以由足智多谋的个人或群体从反复发生的自然疫情中获得。目前没有药物可用于预防或治疗MARV感染。对MARV免疫保护剂的需求显然未得到满足，以应对生物战以及由经常发生的自然暴发引起的公共卫生关切。抗体被动免疫已被证明对多种影响人类的病毒、细菌、真菌和寄生虫疾病有效。该提案的产品开发目标是Mapp生物制药公司和美国陆军传染病医学研究所的合作，目标是：(1)产生一组全人类抗marv单克隆抗体；(2)根据小鼠模型的疗效选择抗marv单克隆抗体；(3)比较在哺乳动物细胞培养中表达的先导单抗与在快速、低成本、高度可扩展的制造系统中表达的相同单抗的保护效果。除了节省成本外，该系统还提供了快速响应制造能力，可用于解决其他生物防御和新出现和再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。公共卫生相关性：本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战剂，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.