Scientists have identified natural human antibodies that offer protection against three virulent ebolaviruses – those that cause outbreaks in humans. These findings are significant because they could lead to the first broadly effective therapies and vaccines against the deadly disease.
The largest Ebola outbreak in history – the 2013-16 Western African epidemic – killed more than 11,000 people and infected more than 29,000.
Although the disease has now largely vanished from the spotlight, researchers are still working hard to come up with the most efficient vaccines and treatments possible, preparing for any potential future outbreak.
The promise of antibody therapy
Experimental monoclonal antibody therapies – biological therapies which use one type of antibody to bind to and neutralize pathogens – have shown promising results in the fight against Ebola.
However, most of these therapies only target specific ebolaviruses, limiting the impact they can have - doctors would not be able to use them to treat patients in all epidemics.
For example, the most successful therapy tested to date against Ebola virus (the ebolavirus responsible for the latest epidemic) is known as ZMapp. It is made up of three mouse/human chimeric monoclonal antibodies known as c2G4, c4G7, and c13C6. Studies have shown that it could reverse advanced Ebola disease in non-human primates. It also provided initial evidence of efﬁcacy in humans during a phase II clinical trial.
The problem is that it does works against the Ebola virus but not against two related ebolaviruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks in the past.
In a study now published in the journal Cell, the scientists have built on previous research, in which they had identified 349 distinct monoclonal antibodies from the blood of a survivor of the West African epidemic.
Here, they tested these antibodies in tissue culture and in animal models. They found that two of the 349 natural monoclonal antibodies – known as ADI-15878 and ADI-15742 – potentially neutralised infections in all five known ebolaviruses in tissue culture (including Ebola virus, Bundibugyo virus and Sudan virus, the viruses that cause disease in human).
The scientists also discovered that both antibodies offered protection against Ebola virus, Bundibugyo virus and Sudan virus in mice and ferrets. These antibodies could potentially protect humans against all Ebola virus species, but more research is needed to confirm this.
"We believe that these antibodies should protect against all Ebola viruses causing disease in humans. The viruses we know about may only be the tip of the iceberg and it is possible we will see other emerge in future outbreaks but we are optimistic these potent antibodies would work against all ebolaviruses", study co-leader author Kartik Chandran, professor of microbiology & immunology at Albert Einstein College of Medicine, told IBTimes UK.
Studies with non-human primates are currently ongoing, and the results to date look promising, potentially paving the way for clinical trials.
Towards a single vaccine
The scientists have also discovered that the two antibodies work in an unusual way by stopping ebolaviruses from infecting and multiplying within host cells.
ADI-15878 and ADI-15742 bind to the virus while it is still in the bloodstream. The next step for the virus is to enter a membrane around the cells known as lysosome, fusing with it to escape into the host cell's cytoplasm, where it can then multiply.
However, the antibodies appear to be working by preventing the virus from escaping the lysosome, stopping the infection in its tracks.
The scientists think that they could harness these properties to create a single, efficient vaccine against all ebolaviruses, which would work by boosting the levels of ADI-15878 and ADI-15742 in the blood.
"The antibodies we identified worked in an unusual way, targeting a transient form of the virus. There are very few of these antibodies in the blood and we think we could boost them by presenting the right kind of immunogens to the virus. We are hoping our work will also lead to the development of a single vaccine against all major disease-causing Ebola viruses", Chandran said.