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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43AI082744-02
Application #
7787112
Study Section
Special Emphasis Panel (ZRG1-IDM-Q (10))
Program Officer
Repik, Patricia M
Project Start
2009-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$265,356
Indirect Cost
Name
Mapp Biopharmaceutical, Inc.
Department
Type
DUNS #
137551797
City
San Diego
State
CA
Country
United States
Zip Code
92121
Mire, Chad E; Geisbert, Joan B; Borisevich, Viktoriya et al. (2017) Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody. Sci Transl Med 9:
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