An aggressive push to use a second experimental Ebola vaccine to try to help stop the nearly yearlong outbreak in the Democratic Republic of the Congo may have backfired, with the DRC’s health minister insisting the country will not allow use of the vaccine, made by pharmaceutical giant Johnson & Johnson.
The health minister, Dr. Oly Ilunga, had previously suggested a consortium made up of the London School of Hygiene and Tropical Medicine, Doctors Without Borders, and others might be permitted to conduct a clinical trial of J&J’s Ebola vaccine in the country, although not in the outbreak zone, where Merck’s experimental vaccine is being used.
Late last week he rescinded that option, saying the country would not approve a trial of another experimental vaccine during the ongoing outbreak, which has infected more than 2,500 people and killed nearly 1,670.
“There’s a whole debate raging around vaccinations. And we need to close down this debate,” Ilunga said Monday at a World Health Organization meeting called to share updates on the outbreak with partners in the response and donor countries. “We have an effective weapon. … Let’s focus on that.”
That remark seemed to be a rebuttal to Dr. Josie Golding, epidemics lead at the Wellcome Trust, who moments earlier had urged the DRC to reconsider its decision to block use of other vaccines at this time. The Wellcome Trust is part of the consortium.
Golding said the Wellcome Trust strongly believes there is an urgent need to deploy and test the second experimental vaccine, of which there are over a million doses available. “We regret the recent announcement against the use of the J&J vaccine and ask for this to be reconsidered. The lives of the people in North Kivu, across DRC and the region, depend on it,” she said.
Peter Piot, dean of the London School of Hygiene and Tropical Medicine, issued a statement Monday questioning the DRC’s decision, saying his institution trusts “the Minister’s decision [will] be reconsidered.”
But in an interview with STAT, Ilunga appeared unswayed. He criticized the actions of some who want to add the J&J vaccine to the outbreak response arsenal.
“We are in the presence of a very, very dangerous situation. We have people who don’t want to discuss [their plans] with the government. People who have no respect for ethics. And they are ready to introduce a new vaccine and to create new communications problems and trust problems with the community,” he said. “So I just made the decision to say no. We are not going to start a discussion again.”
J&J was more circumspect in its response to Ilunga’s announcement. “We respect the decision of the DRC minister of health regarding Ebola vaccine studies in the country,” Dr. Paul Stoffels, chief scientific officer and the main driver of J&J’s Ebola vaccine effort, said in a statement. “We remain ready to mobilize our resources if we are called on to help with outbreak response efforts.”
Talks have been underway for months among partners in the response about how to use the current outbreak to test unlicensed Ebola vaccines and whether additional unlicensed vaccines could help contain the outbreak.
No Ebola vaccines have yet been licensed in Western countries, though Merck has started the approvals process with the Food and Drug Administration. Russia and China have licensed vaccines, but both countries licensed the products without human effectiveness data to support their use.
Ebola vaccines and therapies have been hindered for years by an unfortunate reality. The only way to test if they actually work is to conduct clinical trials during an Ebola outbreak — a highly challenging time in which to do research.
The unprecedentedly large West African outbreak of 2014-2016 allowed for some clinical trials to take place. But only one — testing the Merck vaccine in Guinea — was able to generate results. The outbreak ended before trials could determine if other experimental vaccines or any of the experimental Ebola drugs worked.
Based on the Guinea trial results, the WHO advised that the Merck vaccine — which is given in a single dose and generates a protective response in about 10 days — should be used in future outbreaks until there is a licensed vaccine. But organizations involved in funding the development of these vaccines such as the Wellcome Trust and CEPI — the Coalition for Epidemic Preparedness Innovations — have been pressing for others to be deployed as well to determine if they work.
In April, the WHO’s vaccines advisory committee, the Strategic Advisory Group of Experts on Immunization, strongly urged that trials of other vaccines be conducted in DRC.
While there has been discussion about whether to test the Chinese or the two Russian vaccines, none of these vaccines is currently available in mass quantities. The only other vaccine for which there is a large supply is the J&J vaccine. And for months discussions have been underway about how and where to use the vaccine.
In late June, it appeared the DRC would be open to the testing of other vaccines. After a two-day meeting in Kinshasa, Ilunga said the country would consider approving applications for vaccine trials so long as Congolese scientists were involved and the vaccines were tested in other parts of the country, not near where Ebola is spreading.
Those pushing for the use of the J&J vaccine had proposed using the vaccine to create a firewall, vaccinating people near but outside the outbreak zone to prevent the virus from spreading into new territory.
But there have been serious concerns raised about the communications and logistical challenges a trial of another vaccine would pose, especially the J&J product, which was designed to be used to prevent outbreaks, not stop them. It must be administered in two doses given nearly two months apart.
Some DRC and NGO officials worried it might be difficult to communicate why some people were getting a one-dose vaccine while others got one requiring two shots, and that the different schedules might give rise to rumors that would erode confidence in and acceptance of the vaccines.
The dosing schedule would be difficult to implement in northeastern DRC, where there are large numbers of displaced people and the population moves about over long distances, Ilunga said.
“How can you, in an environment where people are traveling a lot, where people have no identity card, how can you organize a two-dosage vaccination in rural areas?” he asked. “You vaccinate somebody today and say, ‘Come back two months later.’ … Even from a logistical point of view, it’s not feasible.”
Ilunga said that, instead of modifying the study protocol to take into account the conditions the DRC had set, those designing the study of the J&J vaccine continued to plan for a trial that would also serve as a firewall, citing confidential emails that had been shared with him.
“So they were deliberately ignoring the conclusion of the forum and the decision made by the minister of health,” Ilunga said. “This for me is unacceptable.”
Word of the possible introduction of another vaccine was starting to spread, Ilunga said, with some community leaders asking about it.
He also disputed one of the arguments made to support use of the J&J vaccine — the concern that supplies of the Merck vaccine will may run out before the outbreak is over. Since the vaccination began early last August, more than 162,000 people have been vaccinated with the Merck vaccine.
As of June, there were roughly 500,000 doses currently available, with another 200,000 doses currently in production that should be available next January.
“We are in a very critical outbreak in a very complex environment,” Ilunga said. “We want to have all the human resources dedicated to the outbreak. We don’t want people to be diverted in another clinical trial elsewhere in the country.”
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Oye,
Thanks for sharing much info about this very challenging aspect. I am leaning from your knowledge, however
while I agree with about 90+ percent of what you say I think we must separate the issue of poor governance
and the need for more medicine (vaccine) at this urgent times.
I still do not understand the negative value of if J&J is allow to test, the only other option is more death.(granted Testing is not curing or protecting)
Inform Medics should be making decisions now not government\minister.
The government has a fail history and even if I am not to judge their history I still struggle with the ministers
current decision. I basically see more as better.
While I agree with some of your comment, the article does point out the logistic nightmare of adding another, very different protocol. An epidemic needs more than informed medics. Multiple professionals (epidemiologists, nurses, physicians, government officials, transportation experts, logistic experts, etc.) need to work together because an epidemic, especially of this magnitude, is extremely complex.
I am truly sorry for the general population of in the Congo, that apparently can so easily be swayed to reject disease preventions such as vaccines. Their superstitions must be fed by idiotic zealots who just like to see people suffer and die. But as long as such a scenario is not curbed, then for the sake of humanity on the rest of the globe : travel from that country has to be completely halted. No-one comes out. Until there is acceptance of Ebola counter measurements. And that must include those “governing” that hellish place.
Let us set the records straight.
1. The rVSV-ZEBOV vaccine currently in use in DRC is strictly not been TESTED. That was done in West Africa. It was shown to be efficacious and awaiting licensing.
2. There are other vaccines, on which WHO-SAGE recommended that “opportunities should be sought to assess the efficacy of other candidate EVD vaccines, such as in health care and front-line workers in areas that are not at high risk for EVD and are thus not eligible to receive the rVSV-ZEBOV vaccine. These vaccines include
i. Adenovirus Type 5 Vector (developed by CanSino Biologics Inc., licensed to use under national reserves by NMPA, China in the event of Ebola outbreak or emergency to prevent the Ebola virus disease caused by the Zaïre strain. A EUAL application was submitted to WHO in July 2018 and is currently under review.
ii. GamEvac-Combi and GamEvac-Lyo (developed by Gamaleya Research Institute), licensed in December 2015 by the Ministry of Health of the Russian Federation for emergency use in the territory of the Russian Federation. No EUAL submission was initiated.
iii. Ad26.ZEBOV & MVA-BN-Filo (developed by Johnson & Johnson)’. Phase I/Phase II/Phase I/II/III trials are either completed or on-going to evaluate the safety and immunogenicity of the vaccine regimen Data have been shared with the US FDA and there are plans to submit a dossier to seek licensure under the USFDA animal rule. A rolling EUAL submission was submitted to WHO in July/September 2016 and is annually updated. In parallel, discussions are on with EMEA on the potential of an emergency approval. (This is the vaccine that is the subject of the acrimony
So, Mary F, rVSV-ZEBOV vaccine and the point of DRC Minister of Health is use what works and end this current outbreak, Do all you can to ensure there is enough the vaccine available. That makes sense to me.
Unfortunately, you may need an on-going outbreak to really check the efficacy of Ad26.ZEBOV & MVA-BN-Filo. The question one dares not ask is — well, I am even afraid to ask, but what the heck! the question in the minds of many and especially those at the forefront of the epidemic is: Are they wishing for the continuation of this epidemic so that the efficacy of the two-shot Ad26.ZEBOV & MVA-BN-Filo.can be determined?
and Kathlyn J, like you, I too, am truly sorry for the general population in the Congo, and elsewhere in Africa. However, you assumed (wrongly), that “they can so be easily swayed to reject disease preventions such a vaccine” There are no “idiotic zealots” feeding their superstitions. And nobody likes to “see people suffer and die”. Your comment about those “governing” that hellish place” reminds one of leaders that talk of: shit holes”. The fundamental issue in the “hellish place” is simply the absence of good governance since the COLONIAL days up till today, in DRC and many other African countries. While we in Africa must take the greatest blame for allowing ourselves to be puns in the hands of european countries and the USA, there are CERTAINLY NO saints anywhere in the world!. To me the solution is for Africa to “own” and find solutions to her problems and not depend on “poisonous and poisoned” foreign aid or assistance. Africa has ALMOST all it takes to solve her problems, but she has refused to even take a tiny bit of ALL she has to solve her problems! One problem with Africa is that it STILL prefers to depend on foreigners to solve her problems, instead of using her own genuine people who truly love and care. Be that as it may, my message to our foreign “friends” is if you want to help, ask me what help I need rather than you decide for me what help you think I need.
Looks like I have gone beyond Ebola vaccine. But Ebola vaccine cannot be taken in isolation and out of the realities of the environment
Oyewale
Some people seem to forget that the one-dose vaccine from Merck is being TESTED. So – what happens if that one vaccine does not work? Who could possibly justify the delay for then having to only START with a testing the second vaccine, even if that requires 2 doses? If the “leaders” in the DRC are not open to all the help that is being offered, and if these “leaders” fail to convince their citizens of the need for vaccination – then that says a lot about the DRC, doesn’t it? Hopeless mess.
Dear Al
1. You are right on who is to determine what my illness is. It has to be me explaining to the doctor how I feel and for the doctor to diagnose my illness based on what I tell him or her, and give the correct treatment. Sometimes, with international assistance, the doctor assumes he knows the problem and comes in with a solution based on gut feelings and “i know your problem more than you” attitude
2. It’s really quite easy to understand what the minister concerns are:
he knows his people, he knows his government, he knows the conditions in his country and he says given these conditions you are more likely to bring this outbreak under control using the one shot vaccine, rather than a two shots come back later vaccine. Administering a one dose vaccine, (with the logistics, the cultural issues, the politics, the violence) is already a major problem. Using the 2 dose experimental vaccine is doubling and compounding the problem with no control over who comes back for the second dose and the possibility of ending up with results that are uninterpretable. Meanwhile the epidemic rages on. What choice…ramp up production of the one dose vaccine by appropriate means. Of course the faster the outbreak is brought under control, the less the chance of coming up with efficacy results of the two dose experimental vaccine. The PRIMARY issue is bringing the current outbreak to a long expected and awaited end. Getting a second Ebola vaccine is a priority that pales in the face of ending the current outbreak with over 1,600 people already dead, and more still to die
Regarding the issue of rumors, again you are right. It is the problem of the Minister and the government. The underlying issue is mistrust of the government in a country that has not seen good governance from the colonial days till today.
“We have an effective weapon. … Let’s focus on that.”..Ilunga could not have said it better and we have to listen to him. He understands his country better than any “outside helper” and a two-dose vaccination schedule even in a “peaceful” country is at best a nightmare. A person went to a doctor for help, saying he has an ache in his stomach. The all wise doctor says ..No way..what you have is a headache.
Ask me for the help I need and do not determine for me that this is the help I must have. J&J needs to listen to the words of Ilunga. Really, in the face of on-going outbreak and insecurity in DRC, does it not make more sense and easier to up the production of the one shot available vaccine than to begin some experimental studies with a new two-shot vaccine. Ilunga is right, We have an effective weapon. … Let’s focus on that!
Oye,
who is to determine what your illness is, is it the doctor or you. I am not in the health field but I believe you are suppose to explain to the doctor how you feel for the doctor to diagnose you and give the correct treatment. It’s hard to understand what the minister concern(s) is-are:
1) do not do two doses for logistical reasons
2)stick with the vaccine that is already being administer- in medicine you never ever want only one manufacturer
3)rumors — that is concern he should manage not WHO\or anyone else
if you ask me , I’ll say take all the vaccine and help the people, what is the alternative
Given that only the Merck vaccine is being tested and has shown promise, it seems best if the J&J vaccine at least got tested in some willing cohort of people to assess its efficacy. This testing on people can only be reasonably accomplished during an Ebola outbreak so now would be the time, regardless of how difficult the logistics. Even if this vaccine does little or nothing for control of this outbreak, the actual idea of vaccines is to prevent getting disease in the first place. So testing to find the vaccine or vaccines that best immunize against Ebola is important to prevent against future outbreaks as much or more then controlling this epidemic. The fact that multiple vaccines have at least been developed when in the past there have been none gives hope for the future but there has to be testing to find the one(s) that are best. The minister, no matter his intentions, is not doing what is best to guard against future Ebola epidemics. Only widespread vaccination of the population can change that.