Ebola virus (EBOV;also known as Zaire ebolavirus) (family Filoviridae) is among the most lethal infectious agents known, producing sporadic outbreaks of severe, and highly lethal hemorrhagic fever in humans and nonhuman primates (NHPs). Owing to high morbidity and mortality rates in natural outbreaks, lack of prophylactic and treatment options, aerosol transmission potential, and their highly virulent nature, Ebola viruses have been identified as both NIAID Category A Priority pathogens and CDC Category A Agents of Bioterrorism. Despite this, the current standard of care is limited to palliative treatment and no therapeutic interventions have been approved against EBOV infection. Among many prophylactic and therapeutic platforms currently under development, monoclonal antibody (mAb) technology has emerged as one ofthe most promising treatment methods. Worldwide, there exist ~100 mAbs against EBOV that have been characterized to varying degrees. Six of these mAbs have demonstrated complete to partial protection of NHPs when administered from 1 to 4- 5 days after lethal infection. The goal of Project 1 is to achieve total protection in NHPs as late as possible in the course of infection with an

Public Health Relevance

This project will translate necessary post-exposure antibody cocktails against Ebola virus (Zaire): immediately from a small, fast-tracked antibody pool, and later from an unprecedented, field-wide, definitive analysis of a pool of almost all antibodies known against Ebola virus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI109762-01
Application #
8654208
Study Section
Special Emphasis Panel (ZAI1-LR-M (J1))
Project Start
2014-03-15
Project End
2019-02-28
Budget Start
2014-03-15
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$1,159,802
Indirect Cost
$160,149
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Qiu, Xiangguo; Wong, Gary; Audet, Jonathan et al. (2014) Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514:47-53
Chen, Gang; Koellhoffer, Jayne F; Zak, Samantha E et al. (2014) Synthetic antibodies with a human framework that protect mice from lethal Sudan ebolavirus challenge. ACS Chem Biol 9:2263-73
Murin, Charles D; Fusco, Marnie L; Bornholdt, Zachary A et al. (2014) Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci U S A 111:17182-7
Schieffelin, John S; Shaffer, Jeffrey G; Goba, Augustine et al. (2014) Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med 371:2092-100