Trials of one of the most promising candidate Ebola vaccines are to begin swiftly in healthy volunteers in Europe, Gabon and Kenya, as funds from the Wellcome Trust enable an international consortium to accelerate development of the VSV Ebola vaccine, rVSV-EBOV. This is the latest in a number of international commitments to fast-track early tests of candidate Ebola vaccines so that they could be available for trial in West Africa by the end of the year, and if successful deployed more widely in 2015.
Almost 5,000 people – all but a few from within West Africa – are known to have died in the unrelenting Ebola outbreak, and the actual toll is likely to stand much higher. In one of many international meetings at the World Health Organisation (WHO) in Geneva last week it was agreed that the rapid development and deployment of an effective vaccine is now an urgent priority. A Â£3.1m (US $5m) grant from the Wellcome Trust will allow several global partners, overseen by the WHO, to gather essential safety data for rVSV-EBOV, which had been tested only in monkeys prior to this outbreak.
Funds will also be used to rapidly assess the human response to the vaccine and determine the optimal dose for its use as a preventative intervention. 800 vials of the vaccine, which was developed by the Public Health Agency of Canada, have been donated by the Canadian Government to be used in these trials.
The National Institutes of Health (NIH) have also announced that concurrent early phase trials of the vaccine have begun in the US. Trials there will assess the safety profile of the vaccine at different doses and compare the immune response induced by one versus two injections. Dr Jeremy Farrar, Director of the Wellcome Trust, said: “Several crucial pieces of the jigsaw are falling into place in terms of the global leadership and action required to turn this epidemic around. Communities in West Africa continue to suffer from the crisis with remarkable fortitude and finally the rich world has committed significant finance and resources to support critical public health measures, and progress in the search for treatments is encouraging. Now, accelerated vaccine development is being properly prioritised too, so we have the best possible chance of a safe and effective vaccine in time to transform our prospects of containing Ebola.” rVSV-EBOV uses an attenuated or weakened version of live vesicular stomatitis virus (VSV). VSV is a pathogen found in livestock and has been used successfully in making other vaccines. It is likely to generate a strong immune response and is being considered for use both for post-exposure prophylaxis as well as general prophylaxis. The gene for the outer protein of the VSV virus is replaced with a segment of the gene for the outer protein of the Zaire Ebola virus species. The vaccine can therefore generate an immune response to Ebola infection but does not cause a vaccinated individual to become infected with Ebola. Its immunogenicity, however, means that side effects will need to be monitored closely, especially given its potential use in countries where even transient fever could be a drawback.
The consortium carrying out the trials will be governed by a Project Steering Committee chaired by the WHO’s Dr Marie-Paule Kieny and consisting of senior scientific members from each institution. These include: University Medical Center Hamburg-Eppendorf, University of Marburg, University of Geneva, University of Tuebingen, University of London, Centre de Recherches Medicales de Lambarene in Gabon (CERMEL) and KEMRI Wellcome Research Programme in Kenya. An independent Chair will oversee the conduct of the trials. 335 healthy volunteers will be vaccinated in total: starting with 20 in Germany, followed by 100 in each of Gabon and Kenya, and then 115 in Switzerland, if the trials proceed as planned.
Given the severity of the situation in West Africa, trials of several candidate vaccines are being fast-tracked at the same time through a globally collaborative effort. The accelerated development of rVSV-EBOV is happening in parallel with initial safety trials and manufacturing of vaccines such as cAd3-ZEBOV, the chimpanzee adenovirus vaccine developed by GSK and NIH being tested in healthy volunteers in the UK, US, Mali and soon in Lausanne.
It is hoped that both vaccines will enter Phase 2/3 trials at the end of this year and early next year in West African regions affected by the outbreak. This announcement is part of a series of multi-million pound measures that have been funded by the Wellcome Trust in response to the epidemic and enabling unparalleled international collaboration across the public, private and not-for-profit sectors to tackle the public health emergency. These include trials of the GSK-NIH vaccine in the UK and Mali, a clinical trials platform in West Africa to fast-track tests of candidate treatments for Ebola and separate trials of convalescent serum as a therapeutic.
The Trust is also supporting public health and humanitarian research into the outbreak, and is committed to helping build Africa’s research capacity in the long term. The current announcement brings the Trust’s total funding of Ebola research to approximately £10m.