A Marburg fever outbreak in Equatorial Guinea is galvanizing efforts to test drugs and vaccines for a virus that currently has none. But every day counts, warned experts who gathered virtually on Tuesday to try to chart a course for the work.
The outbreak is believed to have begun in early January, but the confirmation that the Marburg virus was responsible for the growing cluster of people sick with hemorrhagic-fever-like illness was only confirmed on Monday. To date, nine people have died; all were epidemiologically linked. Another 16 people with some symptoms are in quarantine.
There are a number of experimental vaccines and drugs that have been shown in animals to prevent or treat Marburg, a deadly cousin of the deadly Ebola virus family. But finding out if they actually work in people requires an outbreak, and Marburg outbreaks are blessedly rare. This is the first one Equatorial Guinea has recorded. While there have been four in the past decade in Ghana, Guinea, and Uganda (which had two), the last Marburg outbreak with cases that numbered in the double digits was in 2012. And even that one only recorded 15 cases.
“I cannot emphasize enough the requirement for speed for doing any trials,” John Edmunds, an epidemiologist from the London School of Hygiene and Tropical Medicine, said during the meeting, which was organized by the World Health Organization.
Edmunds noted that of the 16 known Marburg outbreaks, most have stopped quickly after normal containment measures have been put in place — isolating people who are sick, using protective equipment to safeguard the medical staff looking after them, and performing safe burials on those who die. “All but two have been curtailed almost immediately,” Edmunds noted of the outbreaks.
Nancy Sullivan, director of Boston University’s National Emerging Infectious Diseases Laboratories, agreed, but noted there are factors in this instance that could increase the risk of a larger outbreak.
“The difficulty with predicting where the outbreak will go is that there is more movement in and out of Equatorial Guinea than we have in some of the more remote locations,” said Sullivan, who led the team that designed one of the Marburg vaccines that could be tested if authorities in Equatorial Guinea agree to conduct a clinical trial. “And while the [ministry of health] has done a great job tracking cases, I think we would be foolish to assume that no cases have gone undetected.”
The meeting, run by the WHO division that works to spur development for vaccines and therapeutics for epidemic diseases, revealed that while the cupboard isn’t quite bare when it comes to Marburg, it’s not crammed with options either. The meeting was told that efforts will focus only on vaccines that have already been shown to be protective in nonhuman primates.
The WHO and the scientists and organizations that work with it to develop vaccines and drugs like these know from recent experience that every passing day in an outbreak lessens the chance of being able to test these tools in the field. There was a flurry of activity last fall to try to organize trials of vaccines and drugs for the Ebola Sudan virus when an outbreak occurred in Uganda. But the outbreak was contained before the trials could get underway.
For Marburg, the vaccine that is the furthest along, the one Sullivan led the design of when she was at the National Institutes of Health’s Vaccine Research Center, is being developed by the Sabin Vaccine Institute. The vaccine, which was formerly in GSK’s pipeline, has been shown to be safe and to induce an immune response in a Phase 1 trial.
But there are only a few hundred doses of that vaccine currently in vials that could potentially be used in a clinical trial, the meeting was told. Another 20,000 or so doses are stored in bulk, but it would take some time to have that product placed in vials and ready for use.
Public Health Vaccines, which is developing a Marburg vaccine using the same vaccine platform as Merck’s licensed Ebola Zaire vaccine, has roughly 300 doses that could be used in a field trial, said Joan Fusco, the private biotech firm’s chief operating officer.
The largest stock of vaccine targeting Marburg is owned by Johnson & Johnson’s vaccine division, Janssen — which has abandoned its efforts to develop vaccines for Marburg and Ebola. Babajide Keshinro, in clinical development and medical affairs at Janssen, told the meeting the company has about 3,500 doses it would be willing to donate. But that vaccine is given in two doses, 56 days apart — not ideal for an outbreak response. Another potential hitch: The expiration date on some of the Janssen vaccine doses is in April, though Keshinro said it is likely stability testing would show that date could be extended.
There was a bright spot on the therapeutics side, with word that Gilead’s antiviral remdesivir — licensed in the United States for Covid-19 as Veklury — is available for testing. The drug was shown to be effective against Ebola Zaire in a trial in the Democratic Republic of the Congo. As a licensed drug, it could potentially be used off-label.
A Phase 1 trial for another therapeutic option, a monoclonal antibody being developed by Mapp Biopharmaceutical, is underway. But the company has a very limited number of doses — about 30 — Tara Nyhuis, director of clinical operations, told the meeting.
Some of the attendees raised questions about how much is known about whether the vaccines or drugs might be expected to work against all the previously identified strains of Marburg virus. Unlike the Ebola family, which has several species of viruses, Marburg has only one. But within that species there are different strains: Musoke, Raven, and Angola.
While the thinking is that the strains are closely enough related that a vaccine made to target one would protect against the others, it would be good to have data to prove that, a couple of the scientists attending the meeting noted.
Tom Geisbert, a filovirus expert at the University of Texas Medical Branch, told STAT after the meeting he’s not too worried about that issue — unless the virus from Equatorial Guinea turns out to be an entirely new strain of Marburg. The Institut Pasteur in Dakar, Senegal, is sequencing the virus, but has not yet revealed its genetic details.
“If it turns out that the sequence is similar to Angola, or Raven, or Musoke — something on which we have a lot of data — that’s good. Because then we know that the vaccines or treatments will probably work,” said Geisbert. “I think a lot of us will feel better once we know what the sequence is and particularly feel better if it’s close to something that already exists.”