What Ebola Survivor Blood Antibodies Can Reveal About Viral Control and Potential Biologics
It’s 1995 in the Democratic Republic of Congo, and a man is infected with the Ebola virus. Years later scientists would draw his blood and begin to analyze the antibodies in the sample, hoping to find information leading to a cure for Ebola. Now, the recently published results of this study identify antibodies in his blood that can prevent the replication of the Ebola virus.
The findings could be used to design an effective vaccine or a disease treatment that stops future Ebola outbreaks from reaching such high levels. But perhaps just as significant, the results also highlight the potential for scientists to use survivors’ antibodies to find cures to other viral diseases.
The Promise of the mAb114 Antibody
Of all the Ebola survivor blood antibodies examined so far, the mAb114 antibody has the greatest potential to help researchers find effective Ebola treatment and prevention strategies. In one experiment, the antibody was injected into six rhesus macaques that had been infected with Ebola and they were able to fully recover. The antibodies saved their lives even after they had started showing symptoms, which is significant because humans can only be diagnosed with Ebola after symptoms manifest. In another experiment, they received a cocktail comprised of mAb114 and another antibody from the survivor’s blood, mAb100, which served as a vaccine that protected them when they were exposed to the virus.1
It is possible that the antibody could be used to cure Ebola patients, but it is more likely that scientists will need to develop a slightly modified version in order to provide effective treatment. For this, many scientists are using biologics software that that enables the design of altered versions of an antibody that are optimized for disease treatment. The identification of mAb114 also has important implications for scientists trying to find treatments for other viruses. If scientists can identify an antibody from a survivor’s blood that combats the virus, they may be able to design a biologic version that effectively treats the disease.
The researchers who analyzed the Ebola survivor blood antibodies also determined how the mAb114 antibody works to combat Ebola: It recognizes and inactivates the viral glycoprotein that is important for viral fusion with the host cell. One subunit of the glycoprotein (GP1) binds to a receptor protein in the cell, which enables a second subunit (GP2) to mediate the fusion of the viral and host cell membranes. The GP1 subunit is shielded by a mucin-like domain (MLD) until the virus enters the cell, at which point it is removed. Defensive antibodies that bind to the MLD don’t recognize the Ebola virus after it sheds the MLD, so the virus evades detection inside the cell. However, mAb114 recognizes the GP1 after the MLD has been removed, so it can bind to and block the protein, which prevents membrane fusion and viral replication.2
Knowing this mechanism, scientists can design biologic antibodies that exploit the same pathway. Such antibodies could potentially block GP1 the way mAb114 does, inhibit the factors responsible for the removal of the MLD, bind to and block the receptor protein, or prevent the fusion-related activity of the GP2 subunit. There is a wide range of design possibilities to explore and scientists can use biologics software to identify the most promising options and streamline testing. Again, it is important to consider how this same process can be used to find cures for other viral diseases. If scientists can identify an antibody from a survivor’s blood and figure out how it works to prevent viral replication, they can design new biologics that work in a similar way.
The Potential for Using Monotherapy Instead of Cocktails
The identification of a monotherapy—that is, a single antibody that can treat Ebola—also bodes well in the search for a cure. The only other candidate antibody therapy that has been shown to be as effective as mAb114 is the Zmapp cocktail, a combination of three antibodies. However, the cocktail must be injected in massive doses in order to work and it has significant side effects. The dosage of mAb114 that was required to cure the macaques was much lower and had no side effects, so mAb114 monotherapy looks to be a more practical option.
Regardless of the specific benefits of mAb114 over Zmapp, using any monotherapy to treat a disease like Ebola is preferable to using a cocktail. In the event of a sudden Ebola outbreak, it would be much easier to distribute a single antibody therapy than a complex cocktail. Complex cocktails are also more difficult to manufacture, so it might not be feasible to manufacture enough for thousands of Ebola victims. While some argue that using a single antibody instead of a cocktail may be risky because the virus might mutate to evade the antibody, this is less likely to be a problem for acute viral infections like Ebola than for chronic viral infections like HIV because the Ebola virus has less time to acquire mutations.
Future Explorations of Ebola Survivor Blood Antibodies
In total, the researchers identified 349 “antibodies of interest” in the Ebola survivor blood sample.3 Researchers have the opportunity to explore the efficacy of each antibody for the treatment and prevention of Ebola, either alone or in combination with other candidate antibodies. In addition to mAb114, other antibodies may also be used as templates for the design of new biologics to treat Ebola. Researchers who collect blood samples from survivors of other viral diseases will likely generate a similar number of promising antibodies to explore. Modern biologics software will help scientists efficiently sort through this massive amount of data, identify the most important antibody features to incorporate in new designs and accelerate the testing process of candidate therapeutics. Ultimately, biologics based on the antibodies in a survivor’s blood could cure the deadliest viral infections that threaten our world today.
The BIOVIA Biologics Solution provides innovative software that can be used to identify candidate antibodies, streamline testing and accelerate the development process. Whether you’re studying Ebola or another viral infection, it is imperative to develop new treatment strategies as quickly as possible so that a future outbreak can be contained before it develops into a public health emergency. Contact us today to learn more about how our software can help your lab find cures for viral diseases.
- “Ebola survivor’s blood holds promise of new treatment,” February 25, 2016, http://www.nature.com/news/ebola-survivor-s-blood-holds-promise-of-new-treatment-1.19440 ↩
- “Structural and molecular basis for Ebola virus neutralization by protective human antibodies,” March 18, 2016, http://science.sciencemag.org/content/351/6279/1343 ↩
- “Blood From Ebola Survivor Yield Clues For New Vaccines and Antibody Drugs,” February 18, 2016, http://www.forbes.com/sites/luketimmerman/2016/02/18/blood-from-ebola-survivor-reveals-300-antibodies-against-the-deadly-virus/2/#20440b426643 ↩