How Rare antibodies can neutralize many types of Ebola Virus

Ebola virus

Ebola virus can cause a severe, often fatal illness in humans. It can be transferred to people from wild animals and spreads in the human population through human-to-human transmission. It causes severe bleeding, organ failure and ultimately leads to death.

What’s new?

A recent study from the Scripps Research Institute brought weaknesses of Ebola virus into the spotlight. This study demonstrates for the first time exactly how human and mouse antibodies can bind to the virus and stop infection-not only for Ebola virus but for other closely related pathogens as well.

Terrifying ebola virus

Actually, Ebola virus isn’t just one pathogen but five which includes Ebola virus, Sudan virus, Bundibugyo virus, Taï Forest virus and Reston virus. These all virus differ from each other by upto 50 percent different amino acid sequence. This diversity makes it tough to develop broad treatment strategies.

Adding to the threat, all members of the Ebolavirus genus could mutate to escape immune system defenses and fight off drug therapies.

Hence these rare antibodies could be the key ingredients in versatile lifesaving therapeutics capable of neutralizing all members of the Ebolavirus genus.

“This is like understanding how to kill five or six birds with one stone,” says Erica Ollmann Saphire, PhD, professor at Scripps Research and senior author of the new papers, published recently in mBio and the Journal of Infectious Diseases. “The different viruses in the Ebolavirus genus vary in their structure, but all these different viruses have the same outbreak potential. We need a therapeutic approach that can target them all.”

Where this antibody was found?

During their research, researchers found a human antibody called ADI-15878 which was present in the blood of Ebola virus survivor. This rare antibody has the capability to neutralize all five members of the Ebolavirus genus.

The weakness of the Ebola virus

This new research found a site in a virus called  “fusion loop” which is used by the virus to fuse with human cells and initiate infection. these  Antibodies bind to this viral site to neutralize all known ebolaviruses. Targeting this peptide could present an opportunity to develop a universal therapy for infections caused by all five members of the Ebolavirus genus.

How do ADI-15878 works?

To examine the mechanism of these antibodies, researchers used a high-resolution structural technique called X-ray crystallography and modeled the interaction between the antibody and the viral glycoprotein (the protein that enables the virus to infect a cell).

To protect itself from detection of the immune system, Ebola’s glycoprotein is covered with sugars. The team found that  that ADI-15878 binds directly to one of these sugars alongside a paddle-like structure on the fusion loop. Part of the antibody then dips down and binds into a pocket that is normally hidden by another part of the viral glycoprotein.

“It’s really cool to see that this antibody has found a way to bind into a cryptic, conserved pocket despite the proximity of sugars and other pieces of the virus that effectively hide this region from the immune system” says mBio study first author Brandyn West, PhD, a research associate at Scripps Research.

The researchers hypothesize that this action locks two important parts of Ebola’s fusion machinery together, making it impossible for the virus to get into human cells. The fusion loop is a key piece of the Ebola virus entry machinery, so its structure is what scientists refer to as highly conserved–meaning the virus can’t easily mutate the fusion loop to escape immune detection without compromising the ability of the virus to infect cells. If antibodies targeting this structure were included in therapies or elicited through vaccines, these antibodies should provide broad protection.

The next study

The second study was done to show that these rare antibodies are not out of reach.

During their research researchers showed that mouse which had been sequentially immunized with Ebola virus and then Sudan virus also had a broadly protective antibody response. The researchers demonstrate that an antibody, termed 6D6, from this mouse binds to the same region as ADI-15878. The immunization study provides more evidence that this part of the fusion loop is a promising target for vaccine design and therapies.

“Both the human and mouse antibodies were able to neutralize all known types of Ebola,” explains Jacob Milligan, PhD, the research associate at Scripps Research and first author of the Journal of Infectious Diseases study.

Future of the study

It could be possible, the researchers say, for therapeutics to include antibodies that work like ADI-15878. Researchers working on Ebola vaccines could also design molecules that look like this region of the fusion loop. These molecules, called immunogens, teach the human immune system which piece of the virus to target.

“We’re hot on the trail of immunogen design strategies to produce more of these neutralizing antibodies,” Ollmann Saphire says.



The BioScientist

The BioScientist is a platform for biological and biomedical thinker which covers the innovative technologies and scientific discoveries in the field of Biosciences.

Related Articles

Back to top button