July 31, 2015

expert reaction to trial results of VSV-ZEBOV Ebola vaccine in Guinea

Writing in The Lancet journal, a research team has published the results of a trial of an Ebola vaccine developed by the Public Health Agency of Canada and Merck, reporting safety and 100% efficacy.

Prof. Trudie Lang, Director of the Global Health Network, University of Oxford, said:

“Amazing scientific progress in this announcement of interim results, and demonstration that vaccine development and testing can happen at speed when collaborations are pulled together like this and led by the WHO and others.

“This vaccine looks to be an important addition to the armoury, and the ring vaccination approach could be used to limit the spread of the last few cases where there is need the keep the effort up. However, it is not licensed yet – hopefully the regulatory effort can happen with the same speed.

“This also shows how important clinical trials are. We need both drugs and vaccines in place to be ready for the next outbreak. This is a great lesson in what can be done but we need to imbed research into the immediate humanitarian response.”

Prof. Sanjeev Krishna, Professor of Molecular Parasitology and Medicine, St George’s, University of London, said:

“This seems to be a pivotal moment that a great many have worked towards achieving. A safe and effective Ebola vaccine can accelerate elimination of this dreadful disease as well as terminating the current outbreak. As this is a live vaccine, one shot may be good enough. Whilst we are all learning lessons about how to deal with future emerging infections, one message is clear. Co-operation and co-ordination between academics, funders, governments, NGOs, industry and communicators can change the speed at which interventions are delivered safely. One lesson surely should be to make the unprecedented speed of evaluating interventions for outbreaks a norm for the future.”

Prof. Andrew Easton, Professor of Virology, University of Warwick, said:

“The article describes the initial results of a vaccine trial for the prevention of Ebola virus disease and the results are extremely positive and the data show that the vaccine is highly effective at generating protection. The results have been achieved in a very short time due to the use of a ‘ring vaccination’ approach that is similar to the method that was used to successfully eliminate smallpox virus.

“In this approach a ‘ring’ of individuals who have direct or secondary contact with an infected individual are identified and offered treatment. This is a social ring of contacts and is not limited by geography. In the study individuals were vaccinated either immediately or 21 days later to allow an assessment of the efficacy of the vaccine.

“Importantly, the people who received the delayed vaccine were provided with all of the available guidance and assistance to reduce the risk of infection that would normally be given so the vaccine was compared against the current best practices available. After 21 days all participants were vaccinated to ensure that everyone had the opportunity to benefit from any beneficial effect of the vaccine.

“The data show that no individuals receiving the vaccine developed Ebola virus disease when assessed 6 days or longer after the vaccination (anyone developing the disease earlier than this would be considered to have contracted the disease before vaccination). Modelling of the spread of infection in earlier studies has indicated that this type of successful intervention is likely to have a very significant effect on containing the spread of an outbreak. This is a major step forward and is the first evidence for an effective preventative treatment that has the promise of limiting the impact of any future outbreaks.

“More work on the data from this study is required and additional questions remain to be addressed. These include how long the protective effect lasts in recipients of the vaccine and some aspects of safety, though there have been trials in healthy individuals that are very positive with relatively few adverse effects seen.

“Some technical challenges remain such as the requirement to keep the vaccine stored at low temperature but that is not a major impediment and technologies are available to assist with that even in difficult to access parts of the world.

“The results are extremely promising for the prevention of Ebola virus disease in humans.  Its use will not eliminate Ebola virus which is maintained in bats but it has the potential to dramatically reduce its impact on humans in the areas where it exists.

“The people who are likely to benefit immediately from a successful vaccine of this sort are healthcare workers who are at the highest risk when treating patients as evidenced by the very high mortality in that group during the current outbreak. One of the things that remains to be assessed before the vaccine might be considered for use on a large scale population vaccination programme is how long the protective effect lasts. If it is very long then delivery of the vaccine to a larger population could be considered but in reality this is unlikely at this point. The major problem is the very sporadic appearance of Ebola virus in outbreaks which are unpredictable in terms of where and when they might next appear. It is not economically viable in the at-risk countries to pay for mass vaccination at this time unless there is support from other countries. The cost of such a process is likely to be very large so in the immediate future, if this or another vaccine is deemed to be sufficiently safe and effective it is most likely to be deployed as soon as an outbreak is identified to restrict the spread and eliminate the infection.”

Prof. Ian Jones, Professor of Virology, University of Reading, said:

“Of the various candidate Ebola vaccines being tested, that based on recombinant VSV always looked a strong contender and this data proves its effectiveness in a field setting. We might lament the fact it was not pushed into trails earlier but the important thing is that now it has been, and it is both safe and effective. The agenda now moves to monitoring the breadth and longevity of immunity, to stockpiling and to plans for distribution in future outbreaks.”

Prof. Tom Solomon, Director of the Institute of Infection and Global Health, University of Liverpool, said:

“This is very encouraging news. Up until now the only way of controlling Ebola has been through public health measures, such as isolating cases to prevent onward transmission. Now at last we have evidence that vaccination against Ebola may work too. It is a credit to all those who have worked so hard on developing and delivering this study, under difficult circumstances.”

Dr Derek Gatherer, Lecturer, Lancaster University, said:

“This is best possible news in the fight against Ebola. We already knew that experimental Ebola vaccines were safe in volunteers and that those volunteers then produced antibodies that would kill Ebola virus in the laboratory – that was Phases I and II of the vaccine trials process. But this Phase III vaccine trial demonstrates that it works in the midst of an ongoing outbreak.

“The volunteers were all people at risk of Ebola infection because of a previous case to which they had been exposed in their family, neighbourhood or workplace. This is called a “ring” strategy because it attempts to build a protective ring of immune individuals around each confirmed case. Because these individuals can’t contract the disease, further spread is prevented.

“Some of the volunteers were vaccinated 3 weeks after exposure – longer than one Ebola infection’s incubation period. That is what scientists call the “control” – by comparing people vaccinated immediately with those “controls” whose vaccination was delayed, we get some hard statistics that can conclusively confirm that the vaccine really does reduce case numbers. It is, I believe, a major breakthrough. Nevertheless we should be aware that Ebola, like all viruses, evolves and there is no guarantee that our present vaccines will always be effective. However, that ought not to detract from the immense achievement of those involved in this project and the bravery of the trial volunteers.

“The recent reappearance of Ebola in Liberia after several weeks in which no cases were recorded, illustrates how difficult it is to be sure that all Ebola transmission chains are detected. Since there may always be cases that get under the clinical radar, however vigilant the public health surveillance, vaccination may be the only way to ensure that we really do “get to zero” in this outbreak. If we fail to achieve zero cases, the potential for the Ebola virus to evolve into something more persistent in human populations – what epidemiologists call an endemic virus – is very real. That’s why today’s development is so important.”

Prof. Adrian Hill, Director of Jenner Institute, University of Oxford, said:

“This is a superb result in a novel trial design showing that a single dose of the VSV Ebola vaccine can provide high level vaccine efficacy in an outbreak setting. The investigators, public health authorities including WHO, funders and trial participants are to be congratulated on producing these key data in record time.

“The vaccine works very well indeed from about a week after vaccination. The trial showed high efficacy for the remainder of the first month, the period assessed in the study. Future work will need to assess the durability of protection to determine whether this vaccine will be useful for large scale population protection.

“These findings in Guinea provide support for the value of animal models in identifying potential vaccines for human use and suggest that other vaccines already in phase 2 trials should also provide high level efficacy in humans.

“This work on Ebola vaccines illustrates how our current practices in vaccine clinical development, often involving over a decade of cautious assessments, can be accelerated substantially. There is now a need to develop vaccines rapidly for other outbreak pathogens of concern such as those causing MERS, Marburg and Lassa fevers.”

Dr Dan O’Connor, Head of Humanities and Social Science, Wellcome Trust, said:

“The success of the ‘ring’ strategy is a hugely important step forward for research ethics. It shows not only that we can conduct urgently needed, rapid response research during epidemics, but that we can do so in a way that is both ethically sound and responsive to the needs of affected communities.”

Prof. Peter Smith, Professor of Tropical Epidemiology, London School of Hygiene &Tropical Medicine, said:

“The interim results of the trial, using a novel evaluation approach, are very exciting and suggest that the Ebola vaccine tested may be highly effective in protecting against Ebola disease among those in the immediate vicinity of an Ebola case. If these results are confirmed as the trial continues, the ring vaccination strategy may be important not only in contributing to ending the current epidemic, but will also be deployable to contain rapidly any future outbreaks of Ebola disease.”

Dr Jeremy Farrar, Director of the Wellcome Trust, said:

“This trial dared to use a highly innovative and pragmatic design, which allowed the team in Guinea to assess this vaccine in the middle of an epidemic. It is a remarkable result, and one that shows the power of equitable international partnerships and flexibility.

“Our hope is that this vaccine will now help bring this epidemic to an end and be available for the inevitable future Ebola epidemics. This partnership also shows that such critical work is possible in the midst of a terrible epidemic. It should change how the world responds to emerging infectious disease threats.”

Dr Ben Neuman, Lecturer in Virology, University of Reading, said:

“This is big news – the most promising medical development so far in the ongoing race to shut down Ebola. There are some caveats to the study – we don’t know how it works with the immune system to stop Ebola, and the study was small in the sense that there were fewer than 30 cases of Ebola among the group studied despite enrolling thousands of people in the trial. Another minor concern is that pregnant women, who are a high-risk group, and children were not vaccinated due to uncertainty of how the vaccine might affect them. But the concerns are small in comparison to the result – people who got the vaccine did not get Ebola, while a few of the people who opted out of vaccination or whose vaccinations were delayed did catch Ebola.

“Because the vaccine uses a live virus of farm animals to show a key protein from Ebola to the immune system, there were initial concerns whether it would be safe to use in people. The good news is that in the people tested (which excluded pregnant women and children), the vaccine was about as safe as a flu jab.

“Unfortunately, in order to know whether a vaccine has worked, you need to show a difference in infection rate between people who got the vaccine and people who didn’t – called a control group. It was more ethical to delay treatment to the control group than the alternative, which would be to treat people with an ineffective vaccine. I can’t think of a more ethical way to run a fair trial, unfortunately.

“We don’t know how long the effects of the vaccine last, but the best use for this vaccine may be in ring-fencing suspected Ebola cases by vaccinating the people who have had close contact with an Ebola patients including their families and medical workers.”

‘Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial’ by Ana Maria Henao-Restrepo et al. published in the Lancet on Friday 31 July 2015. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/ebola/

Declared interests

Prof. Sanjeev Krishna: involved in Phase I studies of the vaccine being evaluated, and funded by WHO/Wellcome Trust and other funders.

Prof. Tom Solomon: “I am on the Data Safety and Monitoring Committee for a different Ebola vaccine trial, the GSK vaccine.”

Dr Derek Gatherer: funded by Lancaster University’s ECSG Scheme to develop molecular testing for Ebola and related viruses.

Prof. Adrian Hill: Adrian Hill is Director of the Jenner Institute at Oxford University. Oxford University researchers have undertaken clinical trials of five candidate Ebola vaccines over the last year including the VSV vaccine.

Prof. Peter Smith was one of the advisors on the design of the trial and chairs the funding committee for Global Health and Vaccination Research (GLOBVAC) of the Research Council of Norway, which provided initial funding for the trial.

Dr Dan O’Connor and Dr Jeremy Farrar: The Wellcome Trust funded the trial.

Prof. Trudie Lang, Prof. Andrew Easton, Prof. Ian Jones and Dr Ben Neuman declares no interests.