Merck Ebola vaccine Ervebo appears to provide substantial protection

Merck’s Ebola vaccine provided substantial protection to people vaccinated during the 2018-2020 outbreak in the Democratic Republic of Congo, with an effectiveness of 84% in those vaccinated at least ten days before being exposed to the virus, reports a new study. A previous study found that people who had been vaccinated but went on to develop the disease were more likely to survive the infection.

The analysisPublished Tuesday in the journal Lancet Infectious Diseases, it provides the first peer-reviewed assessment of how well the vaccine, Ervebo, works in a challenging real-world setting.

The study’s assessment of vaccine efficacy is lower than the estimate of 100% efficacy resulting from the Ebola Ça Suffit! (Ebola, That’s Enough) trial conducted in Guinea during the final days of the 2014-2016 West African outbreak, or the 97.5% preliminary estimate of effectiveness provided by the DRC National Institute for Biomedical Research (INRB) and the World Health Organization for the first year of the 2018-2020 outbreak in the DRC.

But there were strong suspicions that both estimates were too high to be realistic. No vaccine protects everyone who receives it.

“Certainly when used in a real context, with all the challenges that entails, we expect to see lower effectiveness than the [clinical trial] estimate of efficacy,” Sophie Meakin, lead author of the new study, told STAT in an interview.

“The main conclusion is that the vaccine is highly protective against the development of Ebola virus disease ten or more days after vaccination. And even if it is not as high as the 100% that came from the Ça Suffit! process, that is to be expected.”

The study was conducted by researchers from the DRC Ministry of Health, the INRB, the University of Kinshasa and Doctors Without Borders, known by the abbreviation of the French version of the name, Doctors Without Borders. Meakin is an epidemiologist at the MSF Epicenter, a Paris-based unit focused on epidemiology and research.

A vaccine effectiveness of 84% means that in a group of vaccinated people exposed to the virus, 84% fewer people would develop the disease compared to what would happen in a similar group of unvaccinated people.

The vaccine, which protects against the Ebola Zaire virus, is one of only two approved Ebola vaccines, and the only one recommended for use as an outbreak response because it is given in a single dose. The other Ebola vaccine, made by Johnson & Johnson, is given in two doses, 56 days apart, an unwieldy regimen in an emergency situation. The Merck product is licensed in both the European Union and the United States; the J&J vaccine is licensed in the European Union.

Meakin and her co-authors calculated the vaccine effectiveness estimate based on a database that the DRC Ministry of Health and Doctors Without Borders set up during the 2018-2020 outbreak, the second largest on record. Centered in the conflict-torn provinces in North Kivu and Ituri, on the DRC’s borders with Uganda and Rwanda, there were almost 3,500 confirmed infections and almost 2,300 deaths in that outbreak.

Assessing interventions for Ebola, such as vaccines or drugs, is challenging. Many outbreaks traditionally occur in remote locations, where access to affected communities is limited and outbreaks disappear after a few dozen cases.

The outbreak in North Kivu-Ituri was devastating in terms of the damage it caused among an already embattled population. But the large number of cases provided a significant amount of data that the Ministry of Health and Epicenter have since collected, to try to answer important questions about what works to prevent Ebola, or how best to treat Ebola patients if infection occurs . Meakin said Ebola treatment centers were all asked to collect the same set of data on each patient.

Earlier this year, the two groups published a paper showing that people who received the Merck vaccine but then contracted Ebola had a much lower risk of dying than unvaccinated people, even if they were vaccinated after becoming infected. Although it is believed that full protection from the vaccine will not develop until about ten days after vaccination, the study reported that even people who had been vaccinated two or fewer days before vaccination developed symptoms – in other words, people who were likely to have the disease were incubating when they were vaccinated – were about half as likely to die as unvaccinated people who became infected.

Patients’ HIV status was not part of the data collected, a fact that could have potentially impacted the estimate of vaccine effectiveness. It’s conceivable that the vaccine wouldn’t be as protective for people whose immune systems are compromised, Meakin said; If some of the vaccinated people were HIV-positive or had weakened immune systems due to other health problems, that could have pushed down the efficacy estimate.

Heinz Feldmann, who led the work to develop Ervebo, agreed that this is a possibility, although he noted that a study in macaques infected with a simian equivalent of HIV showed that the vaccine provided solid protection . The paperpublished in 2008, showed that four out of six of these monkeys survived after being exposed to Ebola.

Another possible explanation for the lower estimate of vaccine effectiveness could be a failure of the cold chain, said Armand Sprecher, an MSF doctor who has been involved in Ebola outbreak response for almost 25 years. Vaccines must be stored at a specific temperature before use, which can be difficult in remote areas where electricity can be spotty.

Sprecher cautioned against making too much distinction between the differences in the effectiveness estimates. “What does it mean? It means [the vaccine’s] really good,” he said. “As far as vaccines go, something that has efficacy in the 80s or 90s percent is pretty good. With one dose.”

Feldmann, chief of virology at the National Institute of Health’s Rocky Mountain Laboratories in Hamilton, Mont., expressed some disappointment that the effectiveness estimate was not above 90%. But he noted that it is important to have an estimate available now that reflects how the vaccine works in an outbreak setting, as this should temper expectations.

“I think this 85% or 84% is probably closer to the actual situation,” Feldmann said. “It is a very effective tool for outbreak management.”