Lethal Weapon 24: Fighting Ebola with Human Antibodies

FORT BELVOIR, VA, UNITED STATES

04.29.2016

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Fort Belvoir, Va. - There have been 24 Ebola outbreaks since 1976 though none as deadly as the recent West African epidemic. New research conducted by the Defense Threat Reduction Agency’s Joint Science and Technology Office, uses neutralizing antibodies to reduce mortality rates in Ebola infected animals. This research could inspire medical countermeasures to better protect warfighters, civilians and humanitarian aid workers against future outbreaks.

The Ebola virus can infect humans and primates, causing a hemorrhagic fever with mortality rates up to 90 percent. The recent outbreak, from December 2013 to January 2016, resulted in more than 28,000 cases and 11,000 deaths. Although Ebola poses a high public health threat, no licensed treatment or vaccine for filovirus infection currently exists. Recently, several studies showed that filovirus glycoprotein (GP)- specific neutralizing antibodies can reduce mortality following experimental inoculation of animals with a lethal dose of the Ebola virus.

A basic research project managed by JSTO’s Dr. Ilya Elashvili, and performed in conjunction with Vanderbilt University and the University of Texas Medical Branch at Galveston, isolated a large panel of fully human monoclonal antibodies to Ebola. This research demonstrated efficacy in treatment of experimentally infected animals and clarified the mechanism of filovirus inhibition. The results of this effort have been recently reported in a comprehensive study in the Cell article, “Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.”

The article described how the research team, led by Dr. James Crowe, isolated a panel of antibodies that bind to Ebola virus GP from human survivors. Subsequent studies identified antigenic sites where these antibodies interact. They found that the neutralizing antibodies recognize diverse major antigenic sites on GP.

Single-particle electron microscopy structures of antibody-GP complexes revealed that the neutralizing antibodies bind to Ebola virus GP at regions called the glycan cap, or to a site lower down on the GP in the stem region of the protein.

The researchers found that the epitopes where many of antibodies interact is highly conserved in a range of Ebola virus-species, including Ebola Zaire, Bundibugyo and Sudan. The data obtained through these studies elucidates the mechanism of the virus’ neutralization, as they indicate the human Ebola virus-neutralizing antibodies bind to infectious viruses at the glycan cap and inhibit structural rearrangements necessary for attachment and entry.

The human antibodies were found to be effective to treat otherwise lethal experimental Ebola infection in mice and guinea pigs. This new knowledge could help develop broad-spectrum protective remedies, such as broadly neutralizing antibody and universal structure-based vaccine designs, and detection capabilities against the existing filoviruses and emerging viral strains.

Dr. Crowe’s laboratory is collaborating with academic and industrial partners that are conducting preclinical studies on Ebola antibodies, which could protect warfighters and humanitarian aid workers responding to outbreaks as well as the local at-risk population.

POC: Dr. Ilya Elashvili; [e-mail]

• Date Taken: 04.29.2016
• Date Posted: 04.29.2016 13:21
• Story ID: 196902
• Location: FORT BELVOIR, VA, US