DRC is no stranger to Ebola outbreaks. Why isn’t there a vaccine or treatment to help now?

Repeated Ebola Outbreaks in the DRC: The Quest for Effective Vaccines and Treatments

DRC is no stranger to Ebola – Democratic Republic of Congo (DRC) has faced numerous Ebola outbreaks over the decades, yet the current crisis remains a challenge. A swiftly growing epidemic, which gained global attention just over a week ago, is now classified as the third-largest in history. This outbreak, however, is the 17th to hit the DRC since the virus was first identified there in 1976. Despite its history with the disease, the country still lacks a fully approved vaccine or treatment tailored to the strain responsible for this latest wave.

The Role of the Bundibugyo Strain

The current outbreak is driven by the Bundibugyo strain of the Ebola virus, a variant that has previously caused two smaller epidemics. In 2012, this strain led to 38 confirmed cases and 13 fatalities in the DRC, while an outbreak along the DRC-Uganda border in 2007 reported 131 cases and 42 deaths. These instances, though significant, pale in comparison to the devastation wrought by the Zaire strain, which has been the primary cause of the most severe outbreaks in history.

The Zaire strain was responsible for the 2014-2016 West African epidemic, which claimed over 11,000 lives, and for a major outbreak in the DRC from 2018 to 2020, resulting in more than 3,000 deaths. A vaccine targeting the Zaire strain, named Ervebo, was developed during the West Africa crisis and proved successful in trials. Approved by the US Food and Drug Administration in 2019, Ervebo has been distributed to multiple countries in Europe and Africa, yet its application to the Bundibugyo strain remains untested.

Evaluating the Effectiveness of Existing Vaccines

Dr. Anne Ancia, a WHO representative in the DRC, acknowledged the ongoing debate about whether the Zaire-targeted vaccine could be effective against the Bundibugyo strain. While some experts remain optimistic, others highlight uncertainties. Dr. Thomas Geisbert, a researcher at the University of Texas Medical Branch, noted that early experiments in monkeys suggested the vaccine might offer partial protection. In a 2011 study, he and colleagues administered the Zaire vaccine to four primates and exposed them to the Bundibugyo strain 28 days later. Three of the four survived, indicating a potential 50% efficacy rate, though the data remains limited.

“It’s encouraging,” Geisbert said. “But the safety of using this vaccine in the current outbreak is ‘the $64,000 question.’ You’re darned if you do and darned if you don’t, right?”

Geisbert also raised concerns about the vaccine’s cross-protection. If the immune system has already encountered the Bundibugyo strain, it might not respond as effectively to the Zaire vaccine. “You don’t want to make something worse,” he warned, emphasizing the need for more robust testing before deployment. WHO chief scientist Dr. Sylvie Briand echoed this sentiment, stating that Ervebo is not currently considered the best option for combating the Bundibugyo strain due to “very little evidence of cross protection.”

The Promise of Targeted Solutions

Researchers are now exploring vaccines specifically designed for the Bundibugyo strain. Dr. Vasee Moorthy, a WHO senior adviser overseeing the research and development blueprint, highlighted an experimental vaccine that uses a different approach. Instead of targeting the Zaire strain directly, this new formulation delivers a protein from the Bundibugyo virus via a vesicular stomatitis virus vector, training the immune system to recognize and fight it. Initial tests in nonhuman primates showed promising results, with one dose providing “complete protection” and preventing illness in animals.

Merck, the company behind Ervebo, has already contributed to global efforts by supplying over 500,000 doses to a vaccine stockpile. The firm is prepared to ramp up production if the current outbreak warrants its use. However, the success of Ervebo in the West Africa epidemic and the 2014-2016 crisis does not automatically guarantee its effectiveness against the Bundibugyo strain. Scientists are now racing to fill this gap, drawing on lessons from the recent pandemic and the 2014 outbreak to expedite vaccine development.

Global Collaboration and the Road Ahead

The urgency of the situation has prompted international organizations to collaborate on potential solutions. Merck has pledged to work with UNICEF and the International Coordinating Group on Vaccine Provision to ensure the vaccine stockpile remains viable. Meanwhile, Dr. Moorthy stressed the importance of accelerated research to address the unique challenges posed by the Bundibugyo strain. “The most promising approach is an experimental vaccine tailored for this specific variant,” he explained, underscoring the need for targeted interventions in future outbreaks.

Historically, the DRC’s experience with Ebola has underscored the complexity of the disease. While the Zaire strain has dominated in terms of scale and fatality, the Bundibugyo strain’s emergence in recent years highlights the necessity of diverse strategies. The current outbreak has reignited discussions about whether existing vaccines can be adapted or if new ones must be developed from scratch. With the potential for rapid progress seen during the Covid-19 pandemic, hopes remain high for a solution that can effectively curb this latest crisis.

Why the Delay in Vaccine Approval?

Despite the DRC’s extensive history with Ebola, the lack of a strain-specific vaccine has sparked questions. The Zaire-targeted vaccine, while effective against the most lethal strain, has not been optimized for the Bundibugyo variant. This discrepancy arises from the fact that the virus’s genetic diversity means vaccines must be tailored to each strain’s unique characteristics. The 2014-2016 epidemic in West Africa, for instance, provided critical insights that led to the development of Ervebo, yet the same vaccine has not been tested against the Bundibugyo strain in large-scale trials.

Dr. Ancia pointed out that the decision to use Ervebo in the current outbreak hinges on its safety and efficacy. While the vaccine’s performance against Zaire is well-documented, its cross-protection against Bundibugyo remains unclear. This uncertainty has delayed its approval for the new outbreak, even as scientists work to address it. The challenge is compounded by the fact that the Bundibugyo strain, though less lethal than Zaire, has shown resilience in animal models, with 25% of unvaccinated primates surviving the infection.

A New Era in Ebola Combat

The development of strain-specific vaccines represents a critical step forward in the fight against Ebola. With the Bundibugyo outbreak, researchers are leveraging advancements in immunology to create targeted therapies. The experimental vaccine currently under study, which uses a vesicular stomatitis virus as a delivery system, has demonstrated remarkable success in nonhuman primates. This approach not only offers protection against the Bundibugyo strain but also opens the door to broader applications in future outbreaks.

As the DRC continues to grapple with the current epidemic, the scientific community is under pressure to provide answers quickly. While the existing Ervebo vaccine remains a valuable tool, its limitations against the Bundibugyo strain highlight the need for innovation. The recent success of vaccines during the global pandemic has shown that rapid development is possible, but the unique nature of the Bundibugyo virus means that time and resources must be invested in thorough testing. Until then, the DRC’s fight against Ebola remains a race against the clock, with the stakes as high as ever.