As Ebola spreads, scientists are trying to find vaccines and treatments
As the Ebola outbreak spreads in the Democratic Republic of Congo and Uganda, health workers are rushing to provide supportive care in the hope that some patients will recover on their own, while also isolating the sick and tracing contacts of the infected.
Missing in battle? Vaccines and medicines that could stop the virus. Dismayed by the extent of the spreading epidemic, scientists are scrambling to find it.
On Monday, two major nonprofit vaccine organizations announced tens of millions of dollars in funding for vaccine development. Experts at the World Health Organization have also recommended testing a handful of monoclonal antibodies and other drugs as possible treatments.
Researchers said it would take months to find out whether these measures work. But the treatments will likely still be valuable at this point, as the outbreak will likely continue to rage.
“It will take a long and committed response to bring this outbreak under control,” said Richard Hatchett, the executive director of CEPI, a nonprofit that supports the development of vaccines and other pandemic countermeasures.
One reason Ebola disease is so difficult to control is that it is not caused by a single type of virus. When scientists talk about the “Ebola virus,” they are referring to a type that was first discovered in 1976 in what was then Zaire.
Since then, researchers have identified five additional virus species in the same genus, including one called Bundibugyo virus.
Like the Ebola virus, the Bundibugyo virus causes Ebola disease and results in symptoms such as sudden fever, muscle pain and vomiting. The infection can lead to uncontrolled bleeding and rapid organ failure, killing a significant proportion of patients.
The Bundibugyo virus is responsible for the current Ebola disease outbreak. So far it has only caused two small eruptions since it emerged in 2007.
Most Ebola outbreaks in the last 50 years have been caused by the Ebola virus. Therefore, there are two approved treatments and a vaccine specifically for it and nothing specifically for Bundibugyo virus.
These two types of viruses diverged from a common ancestor a long time ago – probably millions of years ago – and have since evolved in different directions.
So it’s perhaps no surprise that doctors were puzzled when patients showed up at clinics in Africa with Ebola symptoms in April. Diagnostic tests have been developed to detect genetic sequences of the more common Ebola virus. Doctors are just now gaining access to tests that can detect Bundibugyo.
Evolution has changed the molecules called glycoproteins that cover the surfaces of these two viruses. Both species use glycoproteins to attach to and slip into cells.
When people become infected with either virus, their immune system begins producing antibodies that attach to these glycoproteins and block the viruses from infecting cells. If this immune response is strong enough, people can recover from Ebola disease.
To create a vaccine, scientists looked for a way to train the immune system to produce these antibodies. Erbevo, the approved vaccine, consists of a harmless virus called VSV that is engineered to carry Ebola virus glycoproteins that stimulate the production of protective antibodies. In trials in 2014, the vaccine provided 100 percent protection against the Ebola virus.
However, experts doubt that it offers strong protection against the Bundibugyo virus. About a third of the building blocks of the Bundibugyo glycoproteins differ from those of the Ebola virus.
“On the surface, it’s just so different that your immune system perceives it as something different,” said Erica Ollmann Saphire, a virologist at the La Jolla Institute for Immunology in San Diego.
To stop the current outbreak, doctors would have to give people a vaccine that is proven to work specifically against the Bundibugyo virus. That doesn’t exist yet, although scientists have been studying the species since it was first discovered.
This is the gap that CEPI wants to help close. The group will provide up to $61 million to prepare three vaccine candidates for clinical trials.
IAVI, a nonprofit vaccine development organization, will receive up to $3.2 million for a VSV-based vaccine. The group already has experience developing these vaccines against other viruses, including Sudan virus, another species that caused Ebola disease.
Another reason to try this approach is a 2014 study in which scientists tested a VSV vaccine against the Bundibugyo virus on monkeys. It offered 100 percent protection.
Although VSV vaccines have a long history of success, they have one drawback: Scientists must culture the carrier viruses to make the vaccines, a process that can take several months.
A second vaccine based on a different viral vector called adenovirus is currently being developed at the University of Oxford. In 2020, the Oxford team used these adenoviruses to develop a Covid vaccine made by AstraZeneca, which is estimated to have saved over six million lives in its first year of use.
Researchers have created vaccines against other pathogens, including the Sudan virus. “Essentially we’re building on what we’ve already done,” said Teresa Lambe, who is leading the Bundibugyo effort.
CEPI has Dr. Lambe’s team was awarded up to $8.6 million to develop an adenovirus vaccine using bundibugyo glycoproteins. The vaccine is already being manufactured by the Serum Institute of India.
Thanks to the institute’s production capacity and the speed at which adenoviruses grow, researchers say they could have vaccines ready for human clinical trials in one to two months.
But the Oxford researchers have never tested an adenovirus vaccine against the Bundibugyo virus on animals before. Therefore, they must continue to carry out these studies in the coming months.
CEPI is also awarding up to $50 million to Boston-based Moderna to develop an mRNA vaccine for Bundibugyo. Moderna produced one of the two approved mRNA vaccines against Covid during the pandemic.
The company has studied mRNA vaccines for a variety of other diseases. In 2018, Alexander Bukreyev, a virologist at the University of Texas, and his colleagues reported that a Moderna mRNA vaccine protected guinea pigs 100 percent against the Ebola virus.
Moderna’s mRNA vaccines send instructions to our own cells to make proteins that trigger the immune system to produce antibodies. To create a vaccine against the current outbreak, scientists are developing new mRNA molecules that lead to the production of budingbugyo glycoproteins.
Like adenovirus vaccines, mRNA vaccines can be produced quickly. CEPI will help Moderna produce sufficient doses for a large-scale clinical trial if it is proven safe in smaller studies. “In terms of rapidly developing a real countermeasure, this is the best step CEPI can take,” said Dr. Bukreyev.
Gavi, another vaccination nonprofit, also announced Friday that it would commit $40 million to support the manufacturing of leading Bundibugyo vaccine candidates.
There is already an effective treatment for people battling Ebola virus infections. Doctors can inject high doses of particularly effective types of antibodies called monoclonal antibodies.
It turns out that some of these monoclonal antibodies can also attach to the glycoproteins of bundibugyo viruses. On Thursday, an expert panel convened by the WHO recommended sending two monoclonal antibodies into clinical trials.
One of them is called Maftimivab and is part of a three-antibody cocktail made by Regeneron. The other, MBP-134, is an experimental drug developed by San Diego-based Mapp Bio.
In 2017, researchers discovered a pair of antibodies from survivors of an Ebola virus outbreak. Notably, these antibodies can also bind tightly to Bundibugyo virus and Sudan virus glycoproteins.
The researchers then tested MBP-134 on animals. It cured mice and guinea pigs of fatal Ebola virus infections. This success led to preliminary clinical trials that showed the antibodies were safe for humans.
But Mapp Bio has not yet conducted studies to show that MPB-134 cures animals, let alone humans, of Bundibugyo virus.
Dr. James Crowe, a virologist at Vanderbilt University Medical Center who has developed monoclonal antibodies against Covid and other diseases, questioned the decision to focus on these specific treatments. “I don’t think they’re ideal,” he said.
Crowe and his colleagues found highly potent antibodies in blood samples from survivors of the first Bundibugyo outbreak in 2007. In a 2018 study, scientists found that injecting the antibodies into monkeys gave them 100 percent protection against the virus.
But Dr. Crowe was unable to obtain funding to advance the antibodies to the point where they could enter clinical trials. “I made a lot of calls, but no one licensed them,” he said.
The world would be better prepared for outbreaks of pathogens like Bundibugyo if scientists could advance research when there is no public health emergency, Dr. Sapphires.
And instead of trying to make vaccines and drugs that only work against the pathogen that suddenly kills people, researchers could look for treatments that are effective against many related species.
“It’s very simple,” she said. “It just takes leadership, will and funding to conduct clinical trials.”
