The first multi-site trial of an Ebola vaccine has been announced and Professor Beate Kampmann’s team will run the Gambia arm of the trial.
Ebola is a viral illness spread by contact with bodily fluids which can cause fever, vomiting, and severe bleeding. The current outbreak in west Africa has killed more than 1,500 people and the number of people infected is growing. In a bid to stop the spread of the disease, an international team of researchers will conduct trials of a candidate vaccine on healthy volunteers in the UK, the Gambia and Mali.
The University of Oxford is leading the trial and Professor Beate Kampmann from the Department of Paediatrics, Imperial College London will run the trial in the Gambia. Professor Kampmann is an expert in infection and immunity and spends half her time at the Medical Research Council (MRC) Unit in the Gambia where she is in charge of research in vaccinology and has run several vaccination trials, including for prevention of pneumococcal disease, polio and meningitis.
A £2.8 million grant to carry out the trial has been awarded by the Wellcome Trust, the MRC and the UK Department for International Development (DFID). The award was fast-tracked due to the increasing severity of the Ebola situation in west Africa.
What is involved when a research project like this is fast-tracked and does this influence the trial itself?
The big advantage of fast-tracking such an important development is that the funding becomes available more readily. The application itself was done like a normal grant but the review process was speeded up so it was done in just a few days- it was a very unusual timescale. However, no corners are being cut and the stringency of scientific and ethical review for the trial remains the same. We will go through the same ethical and scientific review procedures and there will be the same protocols for patient consent, informing the community and consultations with volunteers and their families.
How many volunteers will take part?
The trial will recruit 60 healthy volunteers from the UK, 40 healthy volunteers from the Gambia and 40 healthy volunteers from Mali. It is vital that we conduct a trial in west Africa where there could be cases in the future and where the trial can be put in the right geographical context. It will also ensure that the studies take into account differences between European and West African populations that might affect safety or the immune response.
Why is it being tested in healthy volunteers, not infected people?
The aim of a vaccine is to prevent the infection or disease to occur in the first place, so by the time people are infected, they need treatment, not vaccination. The vaccine is meant to induce an immune response, which will protect a healthy individual from becoming infected or ill. Vaccine studies happen in several phases and phase I – which is what the Ebola trial is about at this stage – is to establish that the vaccine is safe, which means that there are no major side effects. In order to do this, healthy people need to volunteer to receive the vaccine. In this phase, we can also already gain some information how strong the immune response is which is induced by the vaccine. It would be pretty useless to have a vaccine that is perfectly safe but does not induce the immunity we are aiming for, as it is the immune response which will ultimately protect the individual.
How will the volunteers be recruited in the Gambia?
Effective recruitment is essential to the completion of the trial and we are planning to do this through community networks that we have formed through previous vaccination trials. We won’t offer incentives, but we will provide compensation for travel, work lost and provision of food and healthcare access. In such a resource-poor country we do not want to coax people into the trials for money and from past trials we have learnt that people have a very strong community spirit and want to contribute. They understand the importance of vaccination and how it can save lives in the future.
What will the trial involve?
The trial will be the first test of the vaccine in humans in Africa, following on from safety tests also in volunteers in Oxford and will analyse the safety of the vaccine and the immune response. After vaccination we will follow the volunteers over six months and collect blood samples. The volunteers in the Gambia will stay at the MRC Unit for the first 24 hours for observation. They will then be visited daily over the next several days and after this they will visit the Unit regularly for further sampling and reviews.
How will you analyse the samples you collect?
The MRC Unit in the Gambia has its own laboratories so some of the analysis will be done on site and other samples will be sent off to collaborating laboratories, where all samples from all trial sites can be examined in the same lab and comparisons can be made across sites and individuals. The Unit is very well resourced – it has over 1000 staff, 200 of which are actively involved in research and a number of these are from Imperial. Some samples will also be shipped to the US National Institute of Allergy and Infectious Diseases (NIAID) which is running a parallel study in Uganda on a different vaccination against two species of the virus, Ebola Zaire and Ebola Sudan. The vaccine we will be using is just for the Ebola Zaire species, which is the strain causing the current outbreak in West Africa.
What are the different stages of the trial and what will you be looking for during the six months’ follow up?
Firstly we will be looking for any early immediate side effects which can be both local, such as redness and swelling at the site of injection in the arm, and more systemic, such as fever, headaches and flu-like symptoms. These usually happen in the first days and if they remain mild they are a normal sign that the vaccine is working.
Next we will look at whether the vaccine triggers a response in the immune system. The response is usually not immediate and it takes about one to four weeks as the body works to make antibodies or cytokines and gear up the machinery to fight any “intruders”. Vaccines basically work by tricking the body into thinking the virus is there for real, so it responds with an immune response and this is what we will be looking for in the volunteers. However, it is really important to be clear about the difference between the vaccine and a real infection: the vaccine does not contain any virus that could replicate and make the person ill, just proteins or bits of material which look similar to the virus as far as the immune system is concerned, but cannot make anyone ill or become an Ebola patient.
Finally, up until six months we will be investigating the longevity of the vaccine and whether it creates an immunological memory so people remain immune to the Ebola virus in the longer term or if they may need a booster vaccination at some stage. We will study how long the immune response lasts and whether it decreases at a certain time or becomes ineffective. This follow up period will help us to understand if there is a time when you can boost the response with a slightly modified version of the vaccine.
How does running a trial in west Africa compare with working in the UK?
The main difference lies in the communities we are working with: in the UK, not so many people actually volunteer to actively participate in clinical trials as I have seen in Africa, and we can possibly try and do a better job to engage the public in our research. In Africa, or at least in our communities around the MRC Unit, many people come forward for clinical trials, especially for vaccines, probably because they have seen the benefits of the vaccines in the past for themselves and their children.
Almost all vaccines tested in the Gambia are now part of the national vaccination programme, which is great and remains our goal, if the vaccines are found to work for that community through our research. On the other hand, we need to also make sure that the population really understands what the trials are about and can give informed consent. We have people who do not read or write sometimes, but we have developed systems with the field team, which translate the information into the local languages and explain the studies verbally. People who cannot write themselves then bring an impartial witness to the consent procedure, who can confirm that the person has fully understood the implications for the trial and is happy to participate. This makes the population a bit more vulnerable, and it is important that the procedures are designed with the communities in mind where we wish to enrol. We usually hold wider community consultations before starting the new projects and patient participation and engagement in my view are often better developed in Africa than in the UK.
When are you hoping to start the trial? And when will you have any results that can be shared?
The trials will begin as soon as we receive ethical and regulatory approvals. The UK research teams could start vaccinating volunteers from mid-September but we envisage the trials in the Gambia will start in October. It is hoped that the trials might be finished by the end of 2014 but this will of course depend on many factors. Since it is a multi-centre study, we will work with our partners to get the results out as quickly as possible, and there is a lot of international interest and pressure here, but we hope to have results in early 2015.
How can people volunteer to take part?
In the UK, people can contact the Jenner Institute in Oxford, where the trial is led by Professor Adrian Hill, by emailing email@example.com. At the MRC Unit, the volunteers will be found via our field workers and physicians, following wider community sensitisations.
Why wasn’t the vaccine developed or trialled before now?
The bottom line is probably – and sadly – financial: the market for an Ebola vaccine is small – up till now – and the disease only occurs in resource-poor settings and within countries who could not possibly afford an expensive vaccine. The incentive for pharmaceutical companies to develop a product are therefore very low, as product development, testing and in particular the licensure procedures are expensive and the profit will be small, if any at all.
However, I strongly believe that this is something we need to address as a society and internationally, as we do carry a responsibility for global health. This outbreak again shows how connected the world is and that a disease outbreak in any given country can affect us all, quite apart from the humanitarian mandate. Maybe the WHO and similar agencies – GAVI for example – need to facilitate certain product developments and then stockpile vaccines for outbreak situations, as global health is at stake here. And Ebola is just one example.
Article courtesy of Imperial College London
by Francesca Davenport 04 September 2014 - Link