Ebola Outbreak Sparks Urgent Action in Congo and Uganda

The ongoing Ebola outbreak in the Democratic Republic of Congo and Uganda has prompted health workers to act swiftly, providing supportive care to patients. They’re hoping some might recover independently while also isolating those infected and tracing their contacts.

However, one crucial element is notably missing: effective vaccines and treatments to combat the virus. This has left scientists feeling somewhat desperate as they attempt to address the rapidly worsening situation.

This past Monday, two prominent nonprofit vaccine organizations revealed plans to allocate tens of millions of dollars towards developing vaccines. Additionally, experts from the World Health Organization have suggested the exploration of several monoclonal antibodies and other pharmaceuticals as possible treatments.

Researchers believe it will take months to determine the effectiveness of these interventions, but these treatments may still be invaluable, as the outbreak seems poised to continue its fierce course.

Long-Term Commitment Needed

“This is going to require a lengthy and sustained response to truly manage the outbreak,” remarked Richard Hatchett, the CEO of CEPI, an organization dedicated to developing vaccines and other pandemic countermeasures.

One significant challenge in fighting Ebola is its complexity; the term “Ebola virus” does not refer to a singular entity. The original Ebola virus was identified in 1976 in what was then Zaire, but researchers have since uncovered five additional virus species within the same family.

One such species, the Bundibugyo virus, also leads to Ebola disease, manifesting symptoms like sudden fevers, muscle aches, and vomiting. In severe cases, it can result in uncontrolled bleeding and rapid organ failure, ultimately claiming a substantial number of lives.

The current outbreak is linked to the Bundibugyo virus, which has only caused two minor outbreaks since its discovery in 2007.

Comparison of Virus Treatments

Historically, most Ebola outbreaks over the last half-century have been caused by the original Ebola virus. This has led to the development of two licensed treatments and one vaccine specifically for this virus, while nothing has been developed specifically for the Bundibugyo virus.

Surprisingly, when patients began presenting symptoms of Ebola in Africa this past April, doctors faced confusion. Diagnostic tests were primarily oriented towards identifying the more prevalent Ebola virus. Only recently have tests capable of detecting Bundibugyo become more accessible.

The evolution of these viruses has resulted in changes to key molecules known as glycoproteins that coat their surfaces. Both virus types use these glycoproteins to attach to cells and infiltrate them.

Once infected, a person’s immune system begins generating antibodies that target these glycoproteins, preventing further infection. Researchers sought ways to prompt the immune system to create these antibodies when developing vaccines. The licensed vaccine, Erbevo, features a harmless virus engineered to present Ebola glycoproteins that provoke antibody production. In trials, this vaccine demonstrated 100% success against the Ebola virus.

Nevertheless, experts are skeptical about its effectiveness against the Bundibugyo virus, as a significant number of building blocks in Bundibugyo’s glycoproteins differ from those in the Ebola virus.

“It’s distinct enough that the immune system might perceive it as something entirely different,” noted Erica Ollmann Saphire, a virologist from the La Jolla Institute for Immunology.

To effectively stop the current outbreak, a vaccine targeting the Bundibugyo virus would be essential—yet no such vaccine exists, despite ongoing research since its identification.

Funding and New Vaccine Development

This is the gap that CEPI aims to bridge, committing up to $61 million for the preparation of three candidate vaccines for clinical trials. IAVI, a nonprofit focused on vaccine development, will receive up to $3.2 million to work on a VSV-based vaccine, building on its experience from developing vaccines for other viruses, such as the Sudan virus.

Researchers are encouraged by a 2014 study in which a VSV vaccine against Bundibugyo provided complete protection in monkeys. However, creating these vaccines involves culturing carrier viruses, a process that can be time-consuming.

Another vaccine is in the works at the University of Oxford, utilizing a different viral vector known as adenovirus. This same team previously developed an adenovirus-based COVID vaccine, which played a significant role during the pandemic.

Dr. Teresa Lambe, who leads the Bundibugyo project, mentioned that they are applying past experiences to this new effort. CEPI has granted her team up to $8.6 million for an adenovirus vaccine carrying Bundibugyo’s glycoproteins, which is already in production at the Serum Institute of India, potentially allowing human trials to start in one to two months.

However, the Oxford group has not yet tested this adenovirus vaccine against Bundibugyo in animals, meaning further studies will be necessary in the coming months. Additionally, CEPI is providing up to $50 million to Moderna for developing a Bundibugyo mRNA vaccine, building on its previous successes with COVID vaccines.

Monoclonal Antibodies Enter the Scene

Interestingly, some monoclonal antibodies used in treating Ebola can also attach to Bundibugyo glycoproteins. Recently, a WHO committee suggested beginning clinical trials on two of these antibodies. One, maftimivab, is part of a trio manufactured by Regeneron, while the other, MBP-134, is an experimental drug developed by Mapp Bio.

In 2017, researchers identified a pair of antibodies from Ebola survivors that can attach to Bundibugyo and even the Sudan virus. Subsequent animal tests revealed that MBP-134 could effectively treat lethal Ebola infections in mice and guinea pigs, leading to preliminary clinical trials that confirmed its safety for human use.

Yet, Mapp Bio has yet to conduct trials that demonstrate MBP-134’s efficacy against Bundibugyo. Dr. James Crowe from Vanderbilt University expressed concerns about prioritizing these treatments. He previously identified powerful antibodies from survivors of the first Bundibugyo outbreak in 2007, achieving 100% protection in monkeys during a 2018 study. However, he has struggled to secure funding to advance these antibodies to clinical trials.

Dr. Saphire believes that better preparedness for future Bundibugyo outbreaks could come from a proactive research approach, rather than waiting for emergencies to prioritize vaccine and treatment development.

In an ideal world, scientists would seek treatments effective against a range of related viruses instead of concentrating only on the specific pathogen causing an outbreak. “This is straightforward,” she remarked, “It hinges on leadership, will, and the financial resources needed for clinical studies.”