FORT BELVOIR, VA, UNITED STATES
FORT BELVOIR, Va. - New developments using monoclonal antibodies (mAbs) to block Ebola infection and even to treat after symptoms appear show promise in protecting warfighters and first responders. DTRA CB/JSTO-funded research by Mapp Biopharmaceutial, Inc. (San Diego, Calif.), working with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID - Frederick, Md.), looked at the design, production, and testing of mAbs targeting the Ebola virus (EBOV) glycoprotein as a means to block the infection process.
Results from this work could ultimately give warfighters and first responders better protection and treatment against Ebola, an issue of increasing importance as human incursions into endemic regions occur more frequently.
It is particularly compelling that the mAbs demonstrated effectiveness in infected primates, even after symptoms developed greater than four days after Ebola exposure (i.e., a realistic “trigger-to-treat” scenario). EBOV is a highly lethal disease that can quickly overwhelm its hosts’ immune system. To rigorously test the potential of their mAbs, scientists implemented a study protocol to mimic a disease treatment scenario, where the initial exposure to an infectious agent, such as Ebola, goes undetected. In this study, none of the infected subjects received the mAbs treatment until clinical signs (fever) and confirmation of the infectious agent (circulating virus particles) could be detected.
The work is detailed in the journal Science Translational Medicine article, “Therapeutic Intervention of Ebola Virus Infection in Rhesus Macaques with the MB-003 Monoclonal Antibody Cocktail,” where the researchers, in collaboration with USAMRIID, used sophisticated telemetry methods to monitor body temperature and a virus diagnostic protocol that detected Ebolavirus in the primates’ blood. The authors point out that, “the ability to treat at a later time point after initial exposure and to mitigate further morbidity and disease pathogenesis underscores the therapeutic potential of mAbs.”
Another benefit to Mapp’s mAbs is that, while originally derived from mice, Mapp has already “chimerized” the murine mAbs with human mAbs. This limits the human immune system from responding to mAbs treatment, thereby improving safety and likely prolonging their effectiveness in humans. With these advances, further study of the mAbs might one day support their advancement into human testing.
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This work, Antibodies improving Ebola survivability, by John Davis, identified by DVIDS, is free of known copyright restrictions under U.S. copyright law.