‘Trojan Horse’ Antibody Attacks Ebola

FORT BELVOIR, VA, UNITED STATES

10.25.2016

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Just as the citizens of Troy unwittingly pulled a wooden horse filled with Greek soldiers into their walled city, researchers deceived Ebola viruses (EBOV), a type of filovirus, into carrying the means of their own destruction.

In a research effort funded by the Defense Threat Reduction Agency’s Joint Science and Technology Office, researchers from the Albert Einstein College of Medicine, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Integrated BioTherapeutics Inc., Vanderbilt University Medical Center and The Scripps Research Institute discovered a new strategy for defeating all five strands of EBOV to protect warfighters and civilians.

Often fatal, EBOV is a disease with no FDA-approved vaccines or treatments. The situation is complicated by five viral strains, four of which cause harm to humans. However, research supported by two JSTO projects has created a novel medical countermeasure design.

Monoclonal antibodies (mAbs) are promising treatments for EBOV patients, but most mAb therapies target individual strains of EBOV with limited effectiveness against the other strains. A research team, led by Dr. John Dye of USAMRIID, sought to discover an effective medical countermeasure for all EBOV strains. The team discovered the Achilles’ heel of EBOV – it must bind to a host-cell protein called Niemann-Pick C1 (NPC1) and multiply in human cells. This new therapeutic strategy targets the weakness shared by all EBOV types. One of the novel antibodies produced under this strategy protected mice against the two most lethal strains, Ebola Zaire and Ebola Sudan.

The team deceived EBOV into carrying the means of its own destruction into cells by synthesizing two types of “bispecific” antibodies (bsAbs), each consisting of two mAbs combined into one molecule. One bsAb neutralized the viral protein that binds to NPC1, the other targeted NPC1. Both had one mAb in common, FVM09, which binds all EBOV while the virus is outside cells, allowing the bsAbs to ride the virus into the cell.

Because the engineered bsAbs block endosomal receptor binding by all filoviruses, combining them with delivery mAbs of viral or cellular origin could afford coverage against all filoviruses, including emerging or engineered variants.

Researcher Dr. Kartik Chandran hopes to extend the ‘Trojan horse’ strategy beyond EBOV for increased warfighter protection.

“We hope that our ‘Trojan horse’ antibody strategy of targeting viruses in lysosomes might work against other disease-causing viruses like flu, dengue, or Lassa, which, like Ebola, also enter host-cell lysosomes as part of their life cycles.”
This breakthrough will increase protection for the warfighter against naturally occurring or engineered viruses.

To read more, please visit the Albert Einstein College of Medicine article, “New ‘Trojan Horse’ Antibody Strategy Shows Promise Against All Ebola Viruses.”

POC: LTC Jurandir Dalle Lucca; [e-mail]

• Date Taken: 10.25.2016
• Date Posted: 10.25.2016 14:02
• Story ID: 212875
• Location: FORT BELVOIR, VA, US