ebola

Researchers funded by the National Institute of Health (NIH) in the US have made a significant step forward in the effort to find a treatment for Ebola Virus Disease (EVD), which was responsible for the recent epidemic in Western Africa (2013 to 2016). More than 28, 000 cases and 11, 000 deaths were reported, making it the worst EVD epidemic since it was first discovered in 1976.

There is currently no Food and Drug Administration (FDA) approved vaccine or therapy for EVD. This has left many African communities vulnerable to future disease outbreaks.

Since the initial case reports of EVD, there has been a surge of research exploring effective immunotherapy strategies which are efficacious against multiple strains of Ebola. NIH funded scientists,Wec et al,  have recently published a breakthrough study in the journal Cell. The researchers examined the blood of a Western Africa Ebola survivor and identified two antibodies (proteins which facilitate the neutralization of foreign organisms such as bacteria and viruses from the body), which may be the key to the development of an EVD immunotherapy.

What is EVD?

EVD is a severe illness with an average fatality rate of 50% and is transmitted by contact with bodily fluids such as blood or semen from infected people. The disease is characterized by sudden onset of flu-like symptoms, which are closely followed by vomiting, diarrhoea, rashes, organ dysfunction and sometimes internal and external bleeding. Treatment of specific symptoms and rehydration are currently the only options available to EVD patients. [1].

NIH study

Zaire Ebola virus, the strain of Ebola responsible for the most recent epidemic, is one of 5 different types of ebolavirus which are part of the family Filoviridae. The investigators screened 349 human monoclonal antibodies [2] and found two candidates, ADI-15878 and ADI-15742, with the potential to eliminate all 5 types of ebolavirus. The investigators discovered that the antibodies recognised the viral glycoprotein (GP) 2, which is located on the virus outer membrane and is responsible for facilitating viral entry into the cell. They predicted that when adhered to the virus, these antibodies would prevent it from invading the host cell and causing an infection.

They tested this theory by treating human cells with the antibodies prior to exposure with different ebolaviruses. As predicted, the antibodies successfully protected the cells from infection from several types of ebolavirus. To further assess whether these antibodies could protect an animal from an Ebola infection, they treated wild type and genetically susceptible mice with the antibodies following infection with Zaire and Sudan Ebola viruses. Again, both mice populations were successfully protected against the viral infection. The investigators also observed a protective effect in ferrets who were infected with Bundibugyo virus, a strain of Ebola virus which caused an EVD outbreak in Uganda in 2007 [3].

Interestingly, as can often happen with antiviral therapy, the Bundibugyo virus became resistant to one of the antibody’s protective effects. A single mutation occurred in the viral genetic code, which conferred viral immunity and allowed it to escape neutralisation.

In an effort to assess the range of this antiviral activity, the investigators also performed laboratory experiments with two related viruses, Lloviu and Marburg. Unfortunately, neither antibody protected human cells against infection from either virus.

Nevertheless, Wec et al have not only identified antibodies that have neutralizing properties against three lethal strains of Ebola virus, but they have also identified a potential target for future vaccines and therapeutics, which may stem any future epidemics. 

 

References:

[1] Bornholdt, Z.A., et al. (2016b). Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak. Science 351, 1078–1083.

[2] Wec  A.C., et al. (2017). Antibodies from a human survivor define sites of vulnerability for broad protection against ebolaviruses. Cell 169, (5), 878 – 890.e15.

[3] https://www.cdc.gov/vhf/ebola/outbreaks/history/summaries.html