The news that both the American aid workers who have contracted Ebola have been treated with a secret serum and appear to be making a recovery will answer many calls for why there is no treatment for Ebola. I wish both patients the best possible outcome. But what is this secret serum, why hasn’t it been used before and how does it work?
In fact the “serum” is a mixture of 3 humanised monoclonal antibodies previously selected for inhibiting Ebola replication and shown to protect monkeys from Ebola infection[1]. Crucially, a study last year showed that the antibody mixture could be given post-exposure, that is once someone was already infected, and still result in about 50% protection[2]. “Serum” is an inaccurate description of the product as a naturally occurring serum, for example taken from an animal or someone who has been previously vaccinated (or infected), would contain many antibodies, only some of which would be effective in blocking virus infection. This product is much more defined; it is made of ONLY antibodies that block virus infection so the potency per volume is far higher. An added twist, although it doesn’t relate to how the antibodies work, is that each antibody was produced by expression of the protein in plants, a technology that has the possibility of cheap manufacture.
Making the secret serum. Mice are immunized with Ebola virus, to which they mount a normal immune response. In this case the mice are transgenic and make human not mouse antibodies so down the line, if they are used in man, the antibodies themselves will not cause a reaction. The antibodies are screened for those that inhibit Ebola virus growth and those that show inhibition are isolated. The genes that encode those antibodies are isolated and put into plant cells in such a way that they make human antibodies as part of the growth of the plant. Plants are harvested and crushed and the human antibody in the sap is purified. Now, when infused into infected patients the antibody slows Ebola growth giving the patient a chance to recover. It is not a cure but a very supportive helping hand for a natural recovery. The treatment is part of the field of “therapeutic antibodies” and is already an accepted clinical practice.
Will this now be rolled out in Africa? Alas probably not. Firstly, no-one knows how late in an infection the products would still work. Both aid workers were in the very centres set up to deal with Ebola so couldn’t have been in a more appropriate place. They were diagnosed very quickly and surrendered themselves for treatment. That is not the case in the rural population of western Africa. The product is not FDA approved and was used under a special “compassionate grounds” clause. This would probably not apply in Africa were local consent would need to be sought. And despite the manufacture in plants, which in theory could be growth on almost limitless scale, the product will not be cheap or plentiful in the short term. All of these facts will limit the application of therapeutic antibodies in a real outbreak situation. However, assuming a good outcome an important principle will have been proved and stockpiling of the product for use in future outbreaks may be a realistic possibility.