The Ebola virus causes a severe hemorrhagic fever with a 50-90% case fatality. No vaccines or treatments are available. Because of its extraordinary lethality and the danger of intentional misuse or accidental importation, the Ebola virus is a category A pathogen and a high priority of biodefense efforts. The Ebola virus can be classified by antibody reactivity into four subtypes, two of which (Zaire and Sudan) are the most pathogenic and most frequently linked to human outbreaks. The Sudan subtype has been linked to four outbreaks including the largest Ebola virus outbreak yet documented (Uganda, 2000-2001) and a recent outbreak in Sudan in 2004. Administration of well-characterized, neutralizing monoclonal antibodies can confer immediate protection in case of viral exposure. However, all monoclonal antibodies with efficacy against Ebola virus have been raised to the Zaire subtype and those specific for only one epitope are known to cross-react to the Sudan Boniface strain. None react to the contemporary Sudan Gulu strain. Here we propose to develop and characterize monoclonal antibodies against the Sudan subtype of the Ebola virus (strains Gulu and Boniface). Epitopes will be mapped by protein biochemistry and x-ray crystallography, and antibodies will be tested for efficacy in mouse and non-human primate models. Through an interactive, multidisciplinary effort, we will combine structural and functional studies in order to determine which structural features on GP can elicit potent, neutralizing antibodies and to provide the necessary, fully characterized candidate immunotherapeutics for biodefense. Our extensive preliminary data demonstrate the feasibility of these specific aims.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI070530-05
Application #
7929464
Study Section
Special Emphasis Panel (ZAI1-LR-M (M1))
Program Officer
Repik, Patricia M
Project Start
2006-09-15
Project End
2011-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
5
Fiscal Year
2010
Total Cost
$740,922
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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