Most monkeys given dual therapy survive infection with lethal virus
A new treatment has protected monkeys exposed to live Ebola virus, one of the world’s most fearsome pathogens. The dual therapy being tested for the first time, a combination of three antibodies and the antiviral drug interferon alpha, rescued nine of 12 animals even after they showed symptoms of disease.
“This is a harbinger of the approach to come,” saysDaniel Bausch, an infectious disease physician at Tulane University in New Orleans who wasn’t involved with the research. Scientists will probably go with a cocktail of drugs against Ebola in future testing, he says. “But it’s too early to say precisely what the cocktail should be.”
Ebola is a rare but lethal virus that has spawned human outbreaks across Central Africa since 1976. It apparently crosses from wild animals to people via exposure to wild game carcasses, causing hemorrhagic disease and high death rates. Neither a vaccine nor a treatment is available.
But 2012 was a promising year in the fight against Ebola. Researchers at U.S. and Canadian government labs reported partial success in saving lab monkeys from Ebola using antibody-based treatments as late as two days after exposure to the virus.
The Canadian team, at the National Microbiology Laboratory in Winnipeg, now reports that combining the antibodies with interferon alpha allowed seven of eight monkeys to survive even when treatment came three days after exposure. Two of four other monkeys survived after getting a combination in which the antibodies were given four days after exposure.
By the time the monkeys got treated, all were experiencing fever, lethargy or loss of appetite, says study coauthor Gary Kobinger, a virologist. These symptoms might be more directly relevant to humans than the number of days postexposure. “Now we know that we can wait until seeing fever and other clinical signs,” he says, and potentially still rescue a person. But Kobinger acknowledges the clock is ticking after Ebola exposure: “Virus replication is exponential, so it’s clear that at some point we will reach a point of no return.”
The interferon alpha shots stimulated a robust immune cell response in the animals and the antibodies, delivered intravenously, blocked virus entry into cells. All monkeys exposed to the virus but not treated died. The report appears in the Oct. 16 Science Translational Medicine.
Kobinger and his team plan to test the safety of the antibodies in people in late 2014 or early 2015. Because of the virus’s lethality, the drug will never be tested in people who have been intentionally infected, he says. So he and other researchers are talking with the World Health Organization about using a combination of experimental drugs in an Ebola outbreak after a safety trial is complete. “We’re telling WHO that everybody has to think very hard about this,” he says. “We are getting into a zone where it could be unethical to not try something” in an outbreak.
X. Qiu et al. mAbs and ad-vectored IFN-alpha therapy rescue Ebola-infected nonhuman primates when administered after the detection of viremia and symptoms. Science Translational Medicine. Vol. 5, October 16, 2013, p. 207ra143. doi: 10.1126/scitranslmed.3006605.
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G.G. Ollinger Jr. et al Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proceedings of the National Academy of Sciences. Vol.109, October 30, 2012, p. 18030.doi: 10.1073/pnas.1213709109.
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