The CDC manufactured a synthetic Ebola virus to test the treatments. It worked



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SSpecialists from Centers for Disease Control and Prevention have created a synthetic version of the Ebola virus circulating in the Democratic Republic of Congo as part of an effort to determine the effectiveness of diagnostic tests and experimental treatments. used in the field.

The research, conducted in the most secure laboratories of the agency – BSL4 – has shown that even though the tests and two of the field treatments were developed on the basis of an earlier variant of the Ebola virus, they continue to be effective against the virus causing the virus. epidemic, the second largest on the disc.

The results, reported Tuesday in the journal Lancet Infectious Diseases, are encouraging, but also raise the question of why outside research groups did not have direct access to viral specimens from the DRC and instead had to create a synthetic version. . The paper noted that no sample of Ebola had been available to the scientific community during the last four outbreaks in the DRC. These outbreaks occurred in 2014, 2017 and 2018.

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The current one, which involved more than 2,400 cases and 1,600 deaths, began last summer.

Scientists who were not involved in the work praised the CDC's efforts, saying it is important to test the tools used against the virus during the outbreak. But they noted that it would be easier, faster and potentially more accurate to use real viruses rather than those recreated from genetic codes stored in an online database.

"I do not know anyone who has isolates from this outbreak," said Tom Geisbert, of the medical branch of the University of Texas at Galveston.

"They have done a great job here in no time, but man, it takes a lot of resources, money and energy to create a cloned virus by reverse genetics. And it would be so much easier if someone had just sent the isolate.

Gary Kobinger, who led the development work of the Ebola ZMapp treatment – one of the therapies tested by the CDC group against the synthesized virus – said that it was becoming increasingly difficult to obtain pathogens to study. It is a worldwide trend, he said, that threatens the world's ability to monitor and develop diagnostic tests for pathogens causing disease.

"Much of the science that benefits them, including diagnoses, is due to the sharing of previous isolates," said Kobinger, director of the Center for Infectious Disease Research at Laval University in Quebec City. about the DRC.

He noted that during the West Africa outbreak of 2014-2016, Guinea had quickly agreed to share virus samples. The Canadian national laboratory, where Kobinger was working at the time, and where the Ebola vaccine currently deployed in the DRC was developed, used virus samples to test whether the vaccine needed to protect against viruses at the same time. origin of this outbreak. It made.

Laura McMullan, the main author of the CDC study, did not know if the agency had requested virus samples from this outbreak. The CDC, in a hurry for a more precise answer, said that the agency had repeatedly offered to help the DRC's National Institute for Biomedical Research with specimen analysis, virus sequencing and assistance to the country. diagnostic. The INRB, as the lab called it, did not ask for help.

"These things are tricky," said McMullan, a researcher with the CDC's Special Viral Pathogens branch, about the processes involved in sharing viral samples. "To obtain material … it is necessary that someone has the will to ship, you must have the appropriate cold chain [equipment]. It is therefore often a problem of logistics. And you must have permission and everyone work together.

A spokeswoman for the DRC's Ministry of Health, Jessica Ilunga, said she would review the country's virus-sharing policy for the outbreak.

McMullan noted that high-quality sequence data generated by the INRB and by scientists from the US Army's Infectious Disease Medical Research Institute, working with the national lab, have been posted online. Access to this data has allowed the CDC team to recreate the virus.

The Congolese team that generated the data analyzed the sequences to try to determine if the tests used to detect the cases and the drugs used to treat them should be effective against the epidemic, publishing their work in Lancet Infectious Diseases in early June. But they used computer programs to do the analysis. The CDC team advanced this work by creating and using a real virus.

This work is important, McMullan said, because genetic sequences can not necessarily predict the actual behavior of a virus.

For example, the study of sequence data showed several points where the tests used seemed potentially incompatible with the virus of the epidemic.

"One of the changes we thought was a significant change," McMullan said. "We noticed the difference and we were" Oh, that could really be a problem. "

In fact, tests have detected the virus of this outbreak as well as the virus causing the West Africa outbreak of 2014-2016. Although both are variants of the Ebola Zaire species, they are slightly different genetically.

Kobinger said that this work was helpful, but that the actual viruses from the outbreak would be even more accurate than those recreated from sequence data. "The best is to have the real deal," he said.

The CDC team found that two of the four treatments used in this outbreak's patients appeared to target the epidemic virus. They tested Gilead's antiviral drug Remdesivir and the ZMapp monoclonal antibody cocktail developed by Mapp Biopharmaceuticals.

McMullan said the team did not have access to the other two treatments, which are also monoclonal antibodies – mAb114, developed by the National Institute of Allergy and Infectious Diseases, and REGN 3470-3471 -3479, manufactured by Regeneron.

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