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Ebola treatment using antibody from survivor's blood passes first trial Ebola treatment using antibody from survivor's blood passes first trial
(6 months later)
A new treatment for Ebola has passed its first test by protecting monkeys from the lethal virus several days after the animals were infected.A new treatment for Ebola has passed its first test by protecting monkeys from the lethal virus several days after the animals were infected.
The therapy uses an antibody that US government scientists collected from the blood of an Ebola patient more than a decade after the person recovered from the disease.The therapy uses an antibody that US government scientists collected from the blood of an Ebola patient more than a decade after the person recovered from the disease.
Early stage trials showed that macaques treated with the antibody developed almost complete protection against a lethal dose of Ebola up to five days after they were injected with the virus.Early stage trials showed that macaques treated with the antibody developed almost complete protection against a lethal dose of Ebola up to five days after they were injected with the virus.
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The antibody, known as mAb114, can now advance in human trials as a potential treatment for the disease which killed more than 10,000 people in the recent, long-running outbreak in Africa.The antibody, known as mAb114, can now advance in human trials as a potential treatment for the disease which killed more than 10,000 people in the recent, long-running outbreak in Africa.
While the West African outbreak, which tore through Sierra Leone, Guinea and Liberia, has been brought under control, there is still no licensed treatment or vaccine against the Ebola. Cocktails of different antibodies, such as ZMapp, and MIL-77, have been used in patients, but how effective they are is unclear. With no reliable therapy at hand, the disease still kills 25 to 90% of those who become infected.While the West African outbreak, which tore through Sierra Leone, Guinea and Liberia, has been brought under control, there is still no licensed treatment or vaccine against the Ebola. Cocktails of different antibodies, such as ZMapp, and MIL-77, have been used in patients, but how effective they are is unclear. With no reliable therapy at hand, the disease still kills 25 to 90% of those who become infected.
In their search for new treatments, a team led by Nancy Sullivan at the National Institute for Allergy and Infectious Diseases in Maryland, took blood from a survivor of the 1995 Kikwit Ebola outbreak in the Democratic Republic of Congo. From this they obtained antibodies that stuck to and neutralised the Ebola virus, meaning that the person’s immune system retained a memory for the virus 11 years after infection.In their search for new treatments, a team led by Nancy Sullivan at the National Institute for Allergy and Infectious Diseases in Maryland, took blood from a survivor of the 1995 Kikwit Ebola outbreak in the Democratic Republic of Congo. From this they obtained antibodies that stuck to and neutralised the Ebola virus, meaning that the person’s immune system retained a memory for the virus 11 years after infection.
The scientists began their tests in macaques by administering the two most potent antibodies, named mAb100 and mAb114. Three monkeys that received injections of the antibodies, starting one day after infection, showed no signs of Ebola symptoms. An untreated macaque given the same dose of Ebola succumbed to the disease after 10 days.The scientists began their tests in macaques by administering the two most potent antibodies, named mAb100 and mAb114. Three monkeys that received injections of the antibodies, starting one day after infection, showed no signs of Ebola symptoms. An untreated macaque given the same dose of Ebola succumbed to the disease after 10 days.
The researchers next tried the most potent antibody, mAb114, on its own. To their surprise, it protected monkeys to the same extent as the dual therapy, even when given five days after infection. The finding, they write in Science, suggests that it may be possible to forgo complex cocktails and use single antibodies to treat the disease.The researchers next tried the most potent antibody, mAb114, on its own. To their surprise, it protected monkeys to the same extent as the dual therapy, even when given five days after infection. The finding, they write in Science, suggests that it may be possible to forgo complex cocktails and use single antibodies to treat the disease.
“There are two reasons we wanted to look at single antibodies. If you have one antibody that gives you protection, it will be far easier to make available in an emergency. But we also wanted to find the virus’s points of vulnerability, and with single antibodies, you can home in on the mechanism for protection,” Sullivan said.“There are two reasons we wanted to look at single antibodies. If you have one antibody that gives you protection, it will be far easier to make available in an emergency. But we also wanted to find the virus’s points of vulnerability, and with single antibodies, you can home in on the mechanism for protection,” Sullivan said.
Jonathan Ball, professor of molecular virology at Nottingham University, said anecdotal evidence that ZMapp and MIL-77 can help Ebola patients has generated plenty of interest in antibodies as therapies against the disease. But while cocktails of antibodies are harder for the Ebola virus to evade through mutation – meaning they could be effective for longer – they are more complicated to manufacture.Jonathan Ball, professor of molecular virology at Nottingham University, said anecdotal evidence that ZMapp and MIL-77 can help Ebola patients has generated plenty of interest in antibodies as therapies against the disease. But while cocktails of antibodies are harder for the Ebola virus to evade through mutation – meaning they could be effective for longer – they are more complicated to manufacture.
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“On the face of it, this is really exciting work, but there are still uncertainties about how effective this approach might be. The virus will find it easier to mutate and escape the killing effects of a single antibody compared to a mixture of three, each targeting a different part of the virus,” Ball said.“On the face of it, this is really exciting work, but there are still uncertainties about how effective this approach might be. The virus will find it easier to mutate and escape the killing effects of a single antibody compared to a mixture of three, each targeting a different part of the virus,” Ball said.
“The antibody cocktails can protect monkeys even when they are given after symptoms develop. This is really important, because humans usually only get diagnosed after symptoms appear. So if the virus doesn’t mutate to stop the antibody working and it works after symptoms develop then it truly is a big step forward,” he added.“The antibody cocktails can protect monkeys even when they are given after symptoms develop. This is really important, because humans usually only get diagnosed after symptoms appear. So if the virus doesn’t mutate to stop the antibody working and it works after symptoms develop then it truly is a big step forward,” he added.
Sullivan said that with chronic infections, such as HIV, there is a danger of the virus becoming resistant through mutations if the drugs are not designed to prevent this from happening. Existing drugs tackle the virus from different directions though, so it effectively has nowhere to hide.Sullivan said that with chronic infections, such as HIV, there is a danger of the virus becoming resistant through mutations if the drugs are not designed to prevent this from happening. Existing drugs tackle the virus from different directions though, so it effectively has nowhere to hide.
But with an acute infection such as Ebola, resistance may be less of a problem, Sullivan said. “With Ebola we don’t yet know. The virus could mutate to resist inactivation by that antibody. When we go forward, we’ll probably do so with two or three antibodies for just that reason. But it’s still nice to know that we could possibly protect with a single antibody if we need to,” she said.But with an acute infection such as Ebola, resistance may be less of a problem, Sullivan said. “With Ebola we don’t yet know. The virus could mutate to resist inactivation by that antibody. When we go forward, we’ll probably do so with two or three antibodies for just that reason. But it’s still nice to know that we could possibly protect with a single antibody if we need to,” she said.