Following a first-ever outbreak of deadly Marburg virus disease in Equatorial Guinea, the World Health Organization (WHO) on Tuesday called an emergency meeting of the Marburg virus vaccine consortium (MARVAC) to receive an urgent update on possible vaccine candidates for the filovirus that can have an 80% fatality rate.  

At the meeting, the agency received updates from five vaccine developers who have been working on candidate vaccines.  WHO experts said that they will soon convene a working group to prioritize existing vaccine candidates, with an eye to seeing if clinical trials for any of the vaccines can be launched in real time, particularly if the outbreak expands.  So far the virus has claimed nine lives, while there are 16 suspected cases in quarantine, and another 15 contacts are under observation.  All cases have occurred in the province of Kie Ntem in the country’s western region.

“The critical next steps include getting full sequence information on the virus, which is being detected in Equatorial Guinea to use that for a number of different purposes,” said Philip R. Krause, chair of the WHO Covid Vaccines Research Expert Group, who led the meeting.

In parallel, WHO will “rapidly” convene a vaccine prioritization committee, Krause said, to “consider updated information from vaccine developers and to simplify, which really means extract relevant sections from the vaccine clinical protocol for potentially use in Equatorial Guinea,” Krause said. He was referring to an already-approved WHO clinical trial protocol for Marburg vaccines, which would likely need adaptation to the context of the current outbreak. 

“Assuming we’ll proceed with clinical studies, and of course this is pending agreement and support from local authorities in Equatorial Guinea, assuming that such a study were to be done, it would be important to convene the prioritization committee to look at these in the context of most up-to-date information – to make decisions about which of these  should be included in in such a study,” Krause said.

The meeting came only a day after WHO officially confirmed the first-ever outbreak of Marburg haemorrhagic fever in Equatorial Guinea. That confirmation came a week after the country’s Health Ministry notified WHO of a suspected case that had first been reported on 7 January in the country’s Kie Ntem province.

Vaccines in the pipeline

At the meeting, the WHO experts reviewed the status of five active vaccine candidates against the virus. Two of the candidates, one developed by the Sabin Vaccine Institute and one by Janssen are in the Phase 1 clinical trials. The other three vaccine candidates being developed by International AIDS Vaccine Initiative (IAVI), Public Health Vaccines (PHV) and Auro Vaccines, are still in the pre-clinical stage of development.

Babajide Keshinro of Janssen said that the company could mobilise 3500 doses of its Marburg vaccine candidate for WHO-led trials immediately in Equatorial Guinea. However, he stressed that the trials would have to begin within the next two months. Beyond that, the company does not yet have a firm estimate on the length of time the Janssen vaccine candidate remains stable.  

Matthew Duchars, speaking on behalf of the Sabin Vaccine Institute, told the committee that the Institute has up to 20,000 doses of active vaccine ingredient, which it was already planning to use for its own Phase2/3 trials later this year. “We have quite a reasonable amount of drug substance, which has been manufactured and is awaiting to be filled, and is probably up to about 20,000 doses from the bulk that’s currently made.”

The Institute also had reserved “slots” with a number of vaccine manufacturers which could be “repurposed” to rapidly produce several hundred finished vials of the vaccine candidate for deployment in Equatorial Guinea. he added.  

Joan Fusco, of PHV, said that their vaccine candidate had just recently secured FDA approval for clinical testing and that they have around 350 vials ready for use. But they do not have further active manufacturing of the product planned at present. 

As for IAVI, Andi Kilansk said that the organization does not have “any available bulk drug, substance or field drug product.” Similarly, Auro Vaccines said it had no Clinical Trial Material (CTM) available at present, and that its own clinical trials had been planned only for later in the year.

In relation to therapeutics, Dr Simon GP Funnell from the United Kingdom’s Health Security Agency, referred to a recent study that found a combination treatment of monoclonal antibodies and remdesivir performed better against the virus than individual drug agents. “A combination of monoclonal antibodies and remdesivir was better than either alone at Day 6. And that’s going to be a theme that’s carried forward,” he said.

Index case on 7 January

The index case of Marburg virus disease occurred on 7 January 2023, Dr George Ameh, country representative of WHO to Equatorial Guinea, told the meeting. However, the Country’s Health Ministry only notified WHO of the case on 7 February, with a definitive lab confirmation of the disease from a Senegalese laboratory on 13 February.

“In total, there have been nine deaths associated with this outbreak, with established epidemiological links. Close family members, those who attended burials of these close family members…nine confirmed deaths as of today. We also have 16 suspected cases in quarantine and 15 asymptomatic contacts being closely followed up from their homes,” he said. 

Despite the month-long lag between the report of the suspected first case and notification to WHO, Dr Matshidiso Moeti, WHO Regional Director for Africa, praised the “rapid and decisive” action by Equatorial Guinean health authorities.

“Marburg is highly infectious. Thanks to the rapid and decisive action by the Equatorial Guinean authorities in confirming the disease, emergency response can get to full steam quickly so that we save lives and halt the virus as soon as possible,” said Moeti.

Marburg virus disease, also known as MVD, is a highly infectious disease that has a fatality ratio that can range between 24% and 88%. The virus, named after a town in Germany where the virus was first identified in 1967 after causing 29 infections and 7 deaths, belongs to the same family of filoviruses as Ebola. The virus is typically transmitted to humans by fruit bats, and then spread between humans through direct contact with bodily fluids of infected people, surfaces and materials.  In Africa, outbreaks have been reported peridically in the Democratic Republic of Congo, Angola, Uganda – but never before in Equatorial Guinea.

Common symptoms of Marburg disease include fever, fatigue, blood-stained vomit and diarrhoea, according to WHO.

“Efforts are also underway to rapidly mount emergency response, with WHO deploying health emergency experts in epidemiology, case management, infection prevention, laboratory and risk communication to support the national response efforts and secure community collaboration in the outbreak control,” stated a WHO press release, published on Monday.

“WHO is also facilitating the shipment of laboratory glove tents for sample testing as well as one viral haemorrhagic fever kit that includes personal protective equipment that can be used by 500 health workers.”

Image Credits: WHO, Megha Kaveri, Alvaro1984 18, Public domain, via Wikimedia Commons.