Recent human studies have reinforced the notion that Merck’s Ervebo vaccine, originally approved for the Zaire strain of Ebola, might also aid in protecting against another strain now causing a fast-spreading outbreak in the Democratic Republic of the Congo.
A new study, published Wednesday in the New England Journal of Medicine following its earlier online release before peer review, adds to the growing body of research suggesting that Ervebo might also be effective against the Bundibugyo strain of Ebola.
This research has spurred increased calls to trial Ervebo in the outbreak area in the DRC, although support from the World Health Organization has been tepid. The WHO is currently focused on testing vaccines specifically for the Bundibugyo strain, which are several months away from clinical trials in the outbreak region.
The WHO, in an email on Wednesday, stated that its Strategic Advisory Group of Experts on Immunization would further investigate this matter at their upcoming meeting in early October.
Edouard Lhomme, lead author of the study and professor at the University of Bordeaux, France, emphasized in an email to STAT, “I believe we have now reached the point where this question should no longer be debated, it should be tested in a carefully designed prospective clinical study.” He stressed the importance of not only developing new vaccines but also quickly assessing the potential of existing ones to save lives.
A related study is reportedly being planned. Bloomberg reported recently that the Africa Centers for Disease Control and Prevention is preparing a trial to test a two-dose vaccine regimen in healthcare workers, with Doctors Without Borders, or MSF, collaborating on the trial. The Africa CDC had not responded to STAT’s inquiries about this study at the time the article was published.
The proposed trial seems to mirror a study conducted on primates over ten years ago, which demonstrated enhanced survival rates in a small number of animals exposed to a lethal dose of Bundibugyo virus after being vaccinated with vaccines targeting the Zaire and Sudan strains. IAVI, an NGO developing a Sudan vaccine using the same platform as Merck’s Ervebo, has doses available and is in talks with Africa CDC about including them in the study.
In an email, IAVI stated, “If there is alignment among the collaborating partners and key authorities in DRC to conduct the study, as well as protocol approval, we intend to supply doses of our investigational Sudan virus vaccine for the trial.”
An international stockpile of vaccines, managed by UNICEF, WHO, and other partners, holds 500,000 doses of Ervebo. Merck expressed via email that it shares the WHO’s concerns regarding the limited evidence supporting cross-protection against the Bundibugyo virus and mentioned that doses from the stockpile can only be released upon UNICEF’s request.
As of Monday, the confirmed cases in the northeastern DRC outbreak were approaching 2,500, with nearly 1,000 fatalities. This makes it the third-largest and fastest-growing Ebola outbreak recorded.
WHO Director-General Tedros Adhanom Ghebreyesus, in an interview last month with STAT, highlighted that political instability, violence, a high number of displaced persons, and distrust of foreign workers complicate containment efforts.
Currently, there are no approved Bundibugyo vaccines, though several NGOs are racing to prepare doses for testing or are conducting preliminary safety and dosage tests — known as Phase 1 trials. However, field trials are still potentially months away.
Although the WHO has indicated that Ervebo could be examined under strict clinical protocols, it expressed concerns that lab observations of cross-protection might not translate into tangible benefits for individuals. The organization cautioned that using the vaccine could create a “false sense of security” among communities and responders, potentially undermining outbreak control efforts and eroding trust in Ebola vaccines for future outbreaks if vaccinated individuals later contract Ebola.
Since the outbreak’s onset, various research groups have analyzed blood samples from individuals vaccinated with Ervebo to check for antibodies against the Bundibugyo virus. Results have varied, but a trend suggests that the vaccine might trigger some cross-protective antibodies. However, researchers advise that only human trials can confirm their protective efficacy.
Isaac Bogach, who authored a modeling study on whether Ervebo could help manage the outbreak, emphasized that clinical trials are essential for answering this question.
“It is highly encouraging that clinical trials of novel Bundibugyo virus vaccines are now underway,” Bogach stated, referencing a Phase 1 trial in the UK conducted by the Oxford Vaccine Group to determine the safest and most effective dose before broader efficacy trials.
“At the same time, the growing body of evidence from animal studies and human immune-response data suggests that existing and licensed Ebola vaccines may provide some degree of cross-protection. Trials evaluating their effectiveness against Bundibugyo virus should be pursued in parallel, particularly given their immediate availability,” added Bogach, an infectious diseases specialist at the University of Toronto.
A commentary, published Monday in The Lancet, also advocates for Ervebo’s clinical trials, citing promising data from the outbreak area. The current Ebola outbreak is in a region previously affected by a significant Zaire ebolavirus outbreak from 2018 to 2020, during which over 300,000 people received the Ervebo vaccine.
Commentary authors noted that as of June 24, only nine out of 1,000 confirmed cases, whose vaccination status was known, had received Ervebo during the previous outbreak, and all nine survived. Of the 242 fatal cases with known vaccination status, none had been vaccinated.
The commentary also referenced unpublished data concerning eight infected healthcare workers who experienced high-risk exposure during surgery on a pregnant woman later identified as an Ebola patient. Of these, three previously vaccinated workers survived, whereas the unvaccinated five did not.
The authors suggested that even if Ervebo provides less protection against Bundibugyo than Zaire ebolaviruses, it could still be beneficial. They compared this to the new malaria vaccine, which, despite not offering full protection, has had a significant impact when combined with other control measures due to the high disease burden.
“If the observed signals of [cross] protection prove genuine, decisions made during this outbreak might be remembered not only for the evidence they generated, but also for the lives they could help save,” said the authors, including prominent DRC Ebola expert Jean-Jacques Muyembe-Tamfum.
There remain uncertainties about Ervebo’s effectiveness in this outbreak. An unpublished study, posted online as a preprint, examined blood samples from around 1,100 people vaccinated in previous outbreaks over five years. It found significant differences in antibody development rates to Bundibugyo virus between two regions, with higher rates near the outbreak’s epicenter.
The modeling study by Bogach and colleagues indicated that the typical ring vaccination strategy — vaccinating contacts and their contacts — might be less effective in this outbreak due to the late detection of many cases after death, complicating contact tracing. The WHO noted that two-thirds of confirmed deaths were of individuals who never sought medical care and were only tested after death.
“Low [case] ascertainment or delayed [contact] tracing could make a biologically active vaccine appear ineffective at population level,” warned the Bogach study.
Ironically, improvements in case detection and contact tracing could significantly aid containment, potentially reducing the perceived efficacy of vaccines in a ring strategy. The modeling suggested that a broader community-wide vaccination approach might have a more pronounced impact.
