Ebola: Clinical trials and tribulation

EBOLAScientists at Vanderbilt University have discovered that antibodies made by Ebola survivors can fight the virus more effectively than antibodies made by people who didn’t survive. Using classical techniques of vaccine production, scientists hope to utilize the antibodies made in the bodies of Ebola survivors to treat the disease.

Vaccines help the immune system to fight fatal diseases by exploiting the ability of the immune system to ‘remember’ infectious organisms and kill them. Vaccines are composed of killed or weakened form of an organism (virus or bacterium) that causes a particular disease. Even though the organism in a vaccine has been altered so that it won’t make us ill, the part of the organism that stimulates the immune system to respond, is still present. This part of the organism is called antigen, and it works specifically to induce the production of antibodies that attack and inactivate the organism you are being vaccinated against.

ZMapp, a drug currently used to treat several Ebola patients, is made of mouse derived antibodies secreted by plasma cells. Scientists now hope to construct the next generation of ZMapp, composed of human antibodies that kill Ebola virus.

To make the drug, scientists isolate antibodies from survivor’s blood. Antibodies contain B-cells. Scientists fuse cancer cells with B-cells and create a hybridoma which pumps out more and more of the antibodies each immune cell originally made. Those antibodies were first tested on African green monkey cells and then on mice. Three of those antibodies were found to effectively protect mice from Ebola, but their mechanism of action is still unknown. To test the safety of these antibodies, FDA started early trials designs in summer 2014.

The first clinical trials of this blood-based Ebola therapy have already started in Liberia, the second most affected country worldwide. Patients are transfused with plasma or blood donated by Ebola survivors. The size of the study is small and it is therefore unlikely to convincingly establish the success of this therapy.

A new trial is about to start in Guinea, the most affected country globally, that will implicate ~300 patients, with a comparison group as. With its greater size, it will aim to evaluate the outcome of the therapy on survival rates 2 weeks after treatment.

Such a therapy, involving convalescent blood and plasma, would seem to be plausible treatments for Ebola, given that tests of ZMapp gave 100% protection against the virus in monkeys and mice. However, plasma is more preferable than blood, because the remaining red blood cells can then be pumped back into the donors’ bodies, survivors can donate a litre of plasma, every two weeks, whereas whole blood can be donated only once every three to four months and because plasma can be preserved for a longer period of time, compared to the whole blood.

Only these clinical trials can establish if the therapy works. If it does, manufacture of convalescent serum will be scaled up straightaway in West Africa.

 

Image: Wikimedia commons

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