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.
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.
|Fusco, Marnie L; Hashiguchi, Takao; Cassan, Robyn et al. (2015) Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs. PLoS Pathog 11:e1005016|