In recent years, Ebola outbreaks have increased in frequency, duration, and geographical spread, underscoring the need for pre- and post-exposure treatments. Antibodies targeting the Ebola virus surface glycoprotein, the viral structure that fuses with host cells, are implicated in protection against lethal disease. However, the characteristics of the human antibody response to Ebola virus surface glycoprotein remain poorly understood. Now, a study from researchers led by The Scripps Research Institute (TSRI) has identified a new group of powerful antibodies to fight Ebola virus. The team state that the antibodies, isolated from the blood of a survivor of the 2014 Ebola outbreak, could guide the development of a vaccine or therapeutic against Ebola; their data also reveal a previously unknown site of vulnerability in the structure of the deadly virus. The opensource study is published in the journal Science.
Previous studies from the lab and other institutions have shown that Ebola virus has several weak points in its structure where antibodies can target and neutralize the virus. However, the immune system typically needs a long period of trial and error to produce the right antibodies against these sites, so researchers have been working with only a small library of anti-Ebola options. Despite this limited library, various studies have had some success in designing antibody cocktails that target several weak points at once. One treatment in development is a cocktail of three mouse antibodies modified to resemble human antibodies. This treatment was successful in primate trials and used as an experimental human treatment in the 2014 outbreak. Therefore, the global medical community are now searching for additional antibodies to fight Ebola. The current study describes the first in-depth view into the human antibody response to Ebola virus, isolating and characterising over 300 monoclonal antibodies that reacted with the Ebola virus surface glycoprotein.
The current study utilised the single B cell isolation platform from Adimab, which the lab used to quickly find more than 300 antibodies that reacted with the Ebola virus surface glycoprotein. Results show that 77% of these antibodies have the potential to neutralize the Ebola virus, and several antibodies demonstrated significant protection against the virus in mouse models. Data findings identified three highly protective antibodies that each targeted a different site, or epitope, on the Ebola virus glycoprotein.
The lab then used electron microscopy to investigate exactly where the antibodies were binding with Ebola virus. The imaging revealed a previously unknown Achilles heel on the virus: a spot at the base of the Ebola virus surface glycoprotein. Results show that while the Ebola virus mutates rapidly, this site is part of the virus’s larger machinery and tends to stay the same which means targeting this spot could neutralize many strains of Ebola.
The researchers explain that because these are human antibodies, not modified mouse antibodies, they potentially could quickly use them to design a treatment. They go on to add that with these new antibodies available, the global community might be able to design secondary treatments in case the Ebola virus mutates to escape other treatments. The group conclude that they have made the genetic sequences of these antibodies available to the global medical community.
The team surmise that the techniques in this study could be used to find treatments for other emerging diseases, such as Zika virus. They go on to note that in just over a year, the combination of Adimab and their methods led to the discovery of promising antibodies, and future experiments should move even more quickly now they have experience with these tools. For the future, the researchers state with other outbreaks, they could take blood samples from the first wave of survivors and potentially produce a therapeutic rapidly, that’s the long-term goal.
Source: The Scripps Research Institute (TSRI)