My cousin, in Philadelphia, tipped me off that I should write a blog article about the current Ebola outbreak that has occurred this year in Western Africa. One of the reasons that this interested him was that the story of the outbreak was being shadowed by another story of a ‘secret’ serum that was being used to treat some of the American victims of the disease. I think ‘Secret’ was the operative word. I had definitely heard about the outbreak, but this was actually the first time that I heard about this serum – and it immediately tipped of my BS / Conspiracy theory detector because of the suggestion that America actually had a secret ‘cure’ for Ebola. It almost begs for allegations by people wearing tinfoil anti-alien hats that America was engineering some Apocalypse Bringing Disease a la I am Legend or Dawn of the Planet of the Apes.
There is currently no vaccine available for Ebola virus infection and the standard of care remains supportive therapy aimed at maintaining the body’s electrolytes, blood pressure and to prevent / treat additional infections that may otherwise complicate care(1). Coupled with an extraordinarily high fatality rate (up to 90%) and horrifying symptoms including internal and external bleeding, fever and
intense weakness, it remains one of the most feared diseases in the world (2). Ebola is so debilitating and deadly, in fact, that its severity has actually functioned to keep it contained within a relatively small area of western Africa. Most cases tend to occur in and around poor, unsanitary hospitals where virus spreads from a contaminated individual or cadaver to a person (often serving as a healthcare worker). Often cases present with symptoms similar to more common, less lethal diseases and are not quarantined away from other patients leading to a rapid accumulation of nosocomial infections (3). One reason for the high mortality rate associated with Ebola infections may be due to a curious condition in which antibodies against the virus may, ironically, worsen the infection. The mechanism of this behavior appears to operate through the binding of antibody to viral glycoproteins, followed by antibody-mediated phagocytosis of virus by immune cells. This is confounding because it is this process that is utilized by immune cells to destroy viruses and may further impair the ability of researchers to develop an effective vaccine as most vaccines work by promoting antibody development (4). With Ebola, the interaction of a protein on the virus’ surface is bound by antibody, which is then bound by an immune cell that internalizes the virus, but instead of destroying the virus, it manages to escape destruction and infect the cell.
To make matters worse, this time around many more people are contracting the disease, so concern is elevated around the world, even some US Congressmen have been making hay about the possibility that undocumented immigrants from Central America may introduce Ebola into the US. Which brings me back to the conspiracy angle. What’s this about a secret serum again?
The serum is actually just an experimental treatment – one that is extremely early in the development process, called ZMapp. This is a product produced by Mapp Biopharmaceutical Inc. that is a combination of three monoclonal antibodies made in tobacco plants (this is a more common method than you might think). The idea being that these antibodies will provide passive protection against Ebola, much like the antibodies produced by a typical vaccine, but -hopefully – without the adverse effects associated with the antibodies that enhance infectivity. Reading the article describing the manufacture of these antibodies does not provide an explanation of how the antibody-mediated enhancement of infection will be evaded, but one may imagine the construction of neutralizing antibodies that lack the constant regions associated with FcR or C1q binding as the binding of these two proteins have been proposed as causing the adverse effect. As this drug lends passive immunity, it may (if effective) prevent infection of an exposed person – or at least lesson the severity of the infection, however it will NOT lead to the accumulation of antibodies by the patient as would a vaccine. Rather, this form of immunity is more akin to treatment with an anti-serum following a snake bite. With luck, a silver lining to this major outbreak may be the opportunity to test an early-stage treatment, possibly resulting in the first ray of hope in improving Ebola survival.