The World Health Organization announced Tuesday it is going to substantially ramp up the number of people eligible to be vaccinated against Ebola in a bid to try contain a dangerous outbreak in the Democratic Republic of the Congo that seems on the cusp of spinning out of control.
Now, people even further removed from individuals who have contracted the virus — an additional ring of contacts — will be offered Merck’s experimental Ebola vaccine. And others in the region who are deemed to be at some but not immediate risk of being exposed to Ebola will be eligible for another experimental vaccine, made by Janssen, the vaccine division of Johnson & Johnson.
Responders, including the WHO and other organizations, will also set up more pop-up vaccination clinics to allow people who want to be vaccinated to go outside their neighborhoods to get the shots. In Butembo and Katwa, the highly charged hot spots of transmission, some people who want to be vaccinated are being threatened for cooperating with the Ebola response, said Dr. Mike Ryan, executive director of the WHO’s emergencies program.
“They want the vaccine,” Ryan told STAT. “The fact that neighbors and other political forces and people are manipulating and threatening and actually punishing families for accepting vaccination is one of the reasons why we’re having to set up pop-up vaccination.”
This outbreak, which is now in its 10th month, has seen 1,585 cases so far and at least 1,045 of the infected have died. Experts worry the outbreak is in an expansion phase which, if unchecked, would see cases spike even faster.
The broadening of the protocols for the vaccination program was approved by the WHO’s expert advisory panel on vaccine, the strategic advisory group of experts on immunization, known as the SAGE.
The changes must still be approved by ethics and scientific committees advising DRC’s health ministry. But professor Jean-Jacques Muyembe, director of the country’s national microbiology laboratory, welcomed the recommendations.
“The DRC Presidential Commission on Ebola highly appreciates the new SAGE recommendations for the [Merck] vaccine,” Muyembe, one of the world’s leading Ebola experts, said in a statement. “This will allow us to address the increasing demand for this vaccine from the communities.”
The expanded vaccination program could end up using hundreds of thousands of doses of vaccine in North Kivu and Ituri, the two provinces in northeastern DRC where this outbreak has raged since last summer. Merck and J&J are donating all the vaccine to the outbreak response.
A few months ago, this plan would have raised concerns that the expanding access would deplete supplies of the Merck vaccine, which is given in a single dose and takes about 10 days to trigger a protective immune response.
But a recent analysis of data from the company that was conducted by the Food and Drug Administration revealed that more doses could be extracted from each vial of vaccine. The effect: There is substantially more of the vaccine available — double at least and, depending how it’s used, even more.
The Merck vaccine was tested and proven to be effective in Guinea during the West African Ebola outbreak of 2014-2016. It is being used in Congo in what’s known as a ring vaccination approach. People who are contacts of cases, and the contacts of those contacts, are offered vaccine. Health workers and other front-line workers — for instance, people who bury patients who die from Ebola — are also offered this vaccine.
Beth-Ann Coller, Merck’s team leader for the vaccine project, explained that when companies make vaccine, they must ensure each vial contains enough viral particles so that each dose is effective, both when the vaccine is freshly made and towards the end of its shelf life.
So they establish a minimum amount, and then a maximum amount — essentially a floor and a ceiling — multiplied by the number of doses each vial will contain. The minimum is the amount that has been shown to be effective; the maximum is the highest dose that can be safely given.
The vaccine was placed into vials at the higher rate, so that even if the vaccine degrades over time, there will always be enough to meet the minimum dose, Coller said.
Merck used as its floor the amount of vaccine given in the clinical trial in Guinea.
But in this case, that means vials of the Merck vaccine contains two times as much vaccine as is necessary to give each person vaccinated the dose that was proven to be effective in Guinea. Reducing the amount used per person will still give each a full dose, but will at least double the number of people who can be vaccinated with each vial, explained Ana Maria Henao Restrepo, who is overseeing the Ebola vaccine project for the WHO.
“It means we have twice as many doses for the contacts and the contacts of contacts,” she said.
The people in the next ring out — the new ring being added to the program — will receive a smaller dose of vaccine. There is data to suggest it will still be protective, but it takes longer for the protection to develop. Henao Restrepo said that’s not a risk with these people, who are further removed from Ebola cases.
The second vaccine that will be deployed, the Johnson & Johnson product, is a two-dose vaccine that was specifically designed to induce long-lasting protection. The company’s plan has been to position the vaccine to be used to protect health workers in advance of Ebola outbreaks. In the early days of Ebola outbreaks, hospitals often amplify transmission because unsuspecting health workers become infected and transmit the virus.
This vaccine will be used outside of the rings of contacts in a bid to build up more immunity in affected communities to try to halt Ebola’s spread.
Dr. Paul Stoffels, J&J’s chief scientific officer, said the company donate enough vaccine to vaccinate 1.5 million people.
Data from multiple studies J&J has conducted suggest that there is some protection after the first dose. For long-term protection, the doses are given on day 1 and then day 60. That schedule — which would be complex to administer in the field — is designed for “peace days,” Stoffels said. “In days of war, which is now with the outbreak of Ebola in such big numbers … we could accept to go to 1 and 30 days, because that has very good efficacy, too.”
Stoffels said he thinks the vaccine could start to be used within a few weeks, pending approval by the DRC government.
The WHO hopes to be vaccinating about 1,000 people a day in coming weeks. At times in this outbreak, vaccination teams have managed to inoculate as many as 800 to 900 people a day. And so far, nearly 112,000 people have been vaccinated. But when violence has rocked affected communities, the response teams have at times been unable to deliver any vaccine.
Dr. Jeremy Farrar, the director of the Wellcome Trust, has been a keen advocate for adding the J&J vaccine to the tools being used to try to contain this outbreak, the second largest on record.
Farrar acknowledged that some of the outbreak response partners are concerned that adding another experimental vaccine, one that requires people to come back for a second injection, will add complexity to already time-consuming vaccination processes.
(Experimental products require what’s known as informed consent. Vaccination teams must explain to recipients that the vaccine isn’t licensed yet and what is known about it. Recipients must then sign documents agreeing to be vaccinated.)
But Farrar said it was also complicated to conduct a clinical trial of the Merck vaccine during the West African Ebola outbreak of 2014-2016 — and yet, it was accomplished.
“Sometimes I think we just have to say: Look, this epidemic is in awful position,” he said. “We’ve got an intervention. A double-dose vaccine. Not perfect, but the best we’ve got. And we should be deploying it.”