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
Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong et al. (2016) Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses. J Virol 90:266-78
Wec, Anna Z; Nyakatura, Elisabeth K; Herbert, Andrew S et al. (2016) A ""Trojan horse"" bispecific antibody strategy for broad protection against ebolaviruses. Science :
Pallesen, Jesper; Murin, Charles D; de Val, Natalia et al. (2016) Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. Nat Microbiol 1:16128
Frei, Julia C; Nyakatura, Elisabeth K; Zak, Samantha E et al. (2016) Bispecific Antibody Affords Complete Post-Exposure Protection of Mice from Both Ebola (Zaire) and Sudan Viruses. Sci Rep 6:19193
Natesan, Mohan; Jensen, Stig M; Keasey, Sarah L et al. (2016) Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses. Clin Vaccine Immunol 23:717-24
Qiu, Xiangguo; Audet, Jonathan; Lv, Ming et al. (2016) Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Sci Transl Med 8:329ra33
Bornholdt, Zachary A; Turner, Hannah L; Murin, Charles D et al. (2016) Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science 351:1078-83
Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu et al. (2016) An Outbreak of Ebola Virus Disease in the Lassa Fever Zone. J Infect Dis 214:S110-S121
Robinson, James E; Hastie, Kathryn M; Cross, Robert W et al. (2016) Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits. Nat Commun 7:11544
Zeitlin, Larry; Whaley, Kevin J; Olinger, Gene G et al. (2016) Antibody therapeutics for Ebola virus disease. Curr Opin Virol 17:45-9

Showing the most recent 10 out of 27 publications