Researchers at The University of Texas Medical Branch at Galveston, in collaboration with Arbutus Biopharma Corporation, have protected nonhuman primates against Ebola Sudan four days following exposure to the virus.
The study results, which were recently published in Nature Microbiology, demonstrated that the treatment was effective at a point when animals have detectable levels of the virus in their system and were at an advanced stage of disease.
"This is a key step in our efforts to protect people from this terrible, lethal disease," said Thomas Geisbert, UTMB professor of microbiology and immunology. "The Ebola virus has five different species and will continue to impact people throughout the African continent, unfortunately with a high mortality rate."
Geisbert noted that significant progress has been made in developing therapeutics against Ebola Zaire, the species responsible for the 2014-15 outbreak in West Africa. However those drugs may not be effective against Ebola Sudan.
"That's why this latest study could be instrumental in reducing Ebola outbreaks," Geisbert said.
Since 2010, Ebola Sudan has been responsible for three outbreaks and until 2014, caused the largest outbreak of Ebola hemorrhagic fever on record, with 425 confirmed cases in Uganda in 2000.
"We were able to protect all of our nonhuman primates against a lethal Ebola Sudan infection when treatment began four days following infection," Geisbert said. "At this point, those infected showed signs of disease and had detectable levels of the virus in their blood."
Although all infected animals showed evidence of serious disease, those receiving the treatment survived and recovered. The untreated controls succumbed to the disease 8-10 days after exposure and had a disease course similar to that reported for Ebola Sudan-infected patients during outbreaks.
The treatment uses a specific short strand of RNA, known as siRNA, designed to target and interfere with the Ebola Sudan virus, rendering it harmless. One of the advantages of this approach is the ability to modify it to different viral species or strains. The siRNAs are delicate, so the researchers encapsulated them using a proprietary lipid nanoparticle (LNP) delivery technology platform developed by Arbutus Biopharma to protect the siRNAs in the bloodstream and allow efficient delivery and cellular uptake by the target cells. This clinically validated technology has been used successfully to protect non-human primates against Ebola Zaire and Marburg virus infection.
"Demonstrating protection in this uniformly lethal model of Ebola Sudan sets a high bar for determining effectiveness, as subjects were infected with a high viral dose that mimics the worst-case scenario of a needle-stick injury with concentrated viral material," said Geisbert. "The survival benefit and rapid control of viral replication with this treatment illustrate the strong potential of this evolving technology platform in combatting lethal viral infections."
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Other authors include UTMB's Joan Geisbert, Krystle Agans, Daniel Deer, Karla Fenton and Chad Mire as well as Amy Lee and Emily Thi from Arbutus Biopharma Corporation in Vancouver, Canada.
The study was supported by the Centers of Excellence for Translational Research, which is an award of up to $26 million over a five-year period from the National Institute of Allergy and Infectious Diseases for a multi-project grant to advance the treatments of Ebola and Marburg virus infections.
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