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After vaccine success, Ebola work must continue

The Merck vaccine needs to be kept at a temperature of – 80°C. Image credit: WHO/S. Hawkey
The Merck vaccine needs to be kept at a temperature of – 80°C. Image credit: WHO/S. Hawkey

The first vaccine to undergo large-scale field trials has shown a 100 % success rate, however the fight against deadly Ebola is far from over, researchers say.

West African states such as Sierra Leone, Guinea and Liberia are facing the biggest ever outbreak of Ebola, a viral infection that causes severe internal bleeding and kills around half the people it infects.

Since the first case in March 2014, over 11 000 people have died during the outbreak, the World Health Organization (WHO) said. The biggest problem is that there is currently no approved vaccine, and almost 900 health workers have also contracted the disease.

However, on Friday last week, researchers announced that a vaccine developed with US drug firm Merck had shown 100 % effectiveness in a so-called Phase III large-scale trial of over 7 000 people in Guinea. It prompted WHO Director-General Margaret Chan to say the vaccine could be a ‘game changer’ in the fight against Ebola.

It is one of a number of potential vaccines being developed for the disease, and researchers say that work must continue.

Among the issues that have yet to be resolved, some vaccines may not be suitable for high-risk people such as the young, pregnant women and those who are HIV-positive, and researchers don’t know yet how long immunity lasts.

The Merck vaccine uses part of the Ebola virus, and is based on a live form of the vesicular stomatitis virus (rVSV), which replicates inside the body of the vaccinated person.

The early stage trial showed it was safe; however, researchers noticed that it caused viral arthritis in around one in five people.

The VSV-EBOVAC project, funded by the EU’s Innovative Medicines Initiative (IMI) public-private partnership, is studying in detail the samples from that early-stage trial in the hope of finding out whether decreasing the dose has an effect on immune responses and the incidence of arthritis.

They’ve also been able to establish that a vaccinated person wouldn’t be likely to infect another person by shedding virus particles.

‘We had to monitor whether the vaccine was shed, and therefore potentially presented a risk for the environment or for contacts of vaccinees … and found that the vaccine, although it replicates in the blood for several days, is not shed: you do not find it in the urine or the saliva,’ said Professor Claire-Anne Siegrist from the University of Geneva in Switzerland, the principal investigator of the Geneva clinical trial.

‘This enables, for example, to immunise the father and not the pregnant mother, with no fear that he will expose her.’

In fact the large-scale trial in Guinea showed that the immunity extended to people who were in close contact with those who had been vaccinated. 'We know this is how vaccines work best,' added Prof. Siegrist. 

Duration of protection

However, one of the big outstanding questions is how long the immunisation remains effective. That’s crucial in the case of vaccinated aid workers or to design a large-scale immunisation programme in an area where Ebola transmission is sustained.

To have a phase III trial planned and executed in what has been a couple of months is completely unprecedented.’

Professor John Edmunds, from the London School of Hygiene and Tropical Medicine, UK

It’s a question that VSV-EBOVAC hopes to answer once enough time has elapsed since the early stage, or Phase I, trial, which started in November last year.

‘We will extend the duration of this clinical study up to 12 months in order to identify the signatures and the determinants of persistent, long-term memory immune responses,’ said project coordinator Professor Donata Medaglini, from the University of Siena, Italy.

Johnson & Johnson is developing a separate Ebola vaccine as part of the EBOVAC project supported by the IMI. It believes its vaccine, which must include a booster shot, could make people immune for longer and also doesn’t have to be kept at very low temperatures like the rVSV-based jab.

The EU is also working with UK-based medicines maker GlaxoSmithKline to develop its vaccine, which has been adapted from a chimpanzee virus, under the EU-funded project EbolaVac.

The work is important as there is a need to come up with vaccines ‘that might be more suitable for vaccination of pregnant women, infant children and the immunocompromised,’ GlaxoSmithKline said in a statement.


These vaccines have been developed at unprecedented speed, and the work being done lays down techniques that could be used in similar fast-moving epidemics.

‘To have a Phase III trial planned and executed in what has been a couple of months is completely unprecedented,’ said Professor John Edmunds, from the London School of Hygiene and Tropical Medicine, who was involved in designing the trial for the Merck and the Johnson & Johnson vaccines.

Normally, large-scale vaccine trials identify an at-risk population, and then test a large number of people.

However, for the Merck vaccine researchers used an innovative technique known as ring vaccination, which concentrates on identifying the contacts of people who have been exposed, and the contacts of those contacts.

‘The trial was specifically designed so that it ought to work in a low-incidence setting, and, of course, it has,’ said Prof. Edmunds. ‘This ring vaccination strategy might well be used for future vaccine trials in these sorts of circumstances.’

Thanks to public health measures in place in infected countries, Ebola cases are falling across West Africa. That’s testament to the work that’s been done on the ground by health workers in isolating infected people quickly and locating people they have been in contact with, but it might make it difficult for vaccine-makers to complete their trials.

It means that Johnson & Johnson has suspended plans for a large-scale efficacy trial in Kambia, Sierra Leone, an area where Ebola virus infection incidence was high until recently. Instead, it is planning to launch a smaller trial in the next few weeks looking at whether vaccinated people in affected countries develop the responses that they believe signify a person is immune.

They hope they’ll be able to get approval based on that, although it might be contingent on them agreeing to continue studying the vaccine effectiveness when it’s in use.

‘Based on all the discussions we have had with the regulator before, knowing that it is very difficult to still do such a (large-scale) study today, I’m rather optimistic that we’ll find a regulatory pathway,’ said Johan Van Hoof, head of research into infectious diseases at Johnson & Johnson division Janssen. ‘It might be linked, however, to some type of post-marketing commitment.’

Many believe that the Merck vaccine should be used to protect those at high risk in areas still affected by Ebola. However, at the moment it doesn't appear that it will be approved by authorities for several months.

The timing means that these vaccines under development are unlikely to have much of an impact on the current epidemic, as long as infection cases continue to dwindle.

‘It may be that the epidemic will have stopped by the time a licensed vaccine becomes available,’ said Prof. Edmunds. ‘It’s a game changer for the future. I don’t think it’s a game changer necessarily for this outbreak.’

Treating the sick

There are a number of research projects underway that are looking at ways to treat people who are already infected with the Ebola virus.

The Ebola_Tx project, funded by the EU, involves giving a newly infected person a transfusion using blood components from someone who has just recovered from Ebola. The project ends in November, and they’ll consider that the technique is effective if they manage to cut the number of deaths by a fifth.

Researchers on the EU-funded REACTION project are also testing Favipiravir, an existing antiviral drug, so that it can be used in this epidemic.

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