The above antibodies identify and neutralize Marburg virus, which inflicts a mortality rate of up to 90%.
Image credit: The Scripps Research Institute
Identified in 1967 among laboratory workers in Uganda who had handled infected animals, Marburg virus was the first of the class of viruses known as filoviruses – which also includes Ebola – to be identified.
The most lethal strain of Marburg emerged in 2004, resulting in an outbreak with a catastrophic fatality rate of 88%. The virus is known to have a mortality rate of up to 90%.
With the world still reeling from the Ebola epidemic of 2014, there is renewed interest in the deadly potential of filoviruses and what treatments may be effective against them.
Previously, researchers from The Scripps Research Institute in La Jolla, CA, had discovered the molecular structure used by the Marburg virus to attach itself to and enter host cells.
Key to defeating the virus is identifying vulnerable sites on the surface of the virus that antibodies can bind to. Studies have found that certain “cocktails” of antibodies can raise an alarm to the immune system and block Ebola virus from entering new cells, so scientists have been investigating similar approaches to tackle Marburg virus.
Earlier this year, the Scripps team reported some success at identifying antibodies effective against one site on Marburg in a study conducted in association with Vanderbilt University in Nashville, TN. In the new study, the Scripps team designed proteins that elicited new antibodies effective against other sites on the virus.
One of these targets was a site that had not been seen in previous studies of the virus. This new site is described as “a wing-like feature” attached to the virus at its base. The antibodies targeting this site were found to be effective at protecting 90-100% of the mice in the study from lethal infection.
The researchers report that the antibodies investigated in the study are also effective against Ebola virus and its four viral relatives.
Antibodies could be used to diagnose Marburg and Ebola mutations
The study’s first author, Marnie Fusco, says that as both Marburg and Ebola are likely to acquire new mutations, “the cross-reactive antibodies could be used as diagnostics for newly emerging strains.”
Cory Nykiforuk, director of pipeline research of Emergent BioSolutions – who initiated the study with the Scripps team 6 years ago – says:
“Understanding where and how the antibodies interact with the virus tells us which regions can be targeted and helps us develop lead candidates for clinical development.
There are multiple filoviruses that threaten our communities, frontline medical workers and defense personnel, and bringing new technologies to the forefront could potentially help meet future requirements.”
Nykiforuk’s predecessor at Emergent BioSolutions, Jody Berry, adds that the “high cost of creating independent vaccines or treatments for each of the different viruses in this family necessitates intelligent design of immunogens (antibody-inducing molecules). The molecular images used to design the molecules and evaluate the antibodies point the way forward.”
Last year, a study published in the open-access journal mBio found that filoviruses such as Marburg and Ebola edit genetic material as they infect their hosts.
Written by David McNamee