Human trials of this candidate vaccine, being co-developed by the US National Institutes of Health (NIH) and GlaxoSmithKline, are to be accelerated with funding from an international consortium in response to the Ebola epidemic, which the World Health Organization recently declared a public health emergency of international concern.
A £2.8 million grant from the Wellcome Trust, the Medical Research Council (MRC) and the UK Department for International Development (DFID) will allow a team led by Professor Adrian Hill, of the Jenner Institute at the University of Oxford, to start safety tests of the vaccine alongside similar trials in the USA run by the National Institute of Allergy and Infectious Diseases (NIAID, a part of the NIH).
The phase 1 trials will begin as soon as they receive ethical and regulatory approvals, which will be considered on an expedited basis. If approvals are granted, the UK research teams could start vaccinating volunteers from mid-September.
The consortium's funding will also enable GSK to begin manufacturing up to around 10,000 additional doses of the vaccine at the same time as the initial clinical trials, so that if the trials are successful stocks could then be made available immediately by GSK to the WHO to create an emergency immunisation programme for high-risk communities.
The candidate vaccine is against the Zaire species of Ebola, which is the one circulating in west Africa, and uses a single Ebola virus protein to generate an immune response. As it does not contain infectious virus material, it cannot cause a person who is vaccinated to become infected with Ebola. Pre-clinical research by the NIH and Okairos, a biotechnology company acquired last year by GSK, has indicated that it provides promising protection in non-human primates exposed to Ebola without significant adverse effects.
Safety trials with small groups of healthy volunteers are now required to ensure that the vaccine does not cause unforeseen side effects, and that it generates a good immune response to Ebola in humans, before it can be rolled out to larger at-risk populations, even on an experimental basis.
To accelerate these trials, the NIH has generously agreed to provide the NIAID/GSK Ebola vaccine for safety studies led by the Oxford team, which will run in parallel to its own trials. Oxford's Jenner Institute has extensive experience of clinical trials of similar vaccines, which they have evaluated clinically for six other diseases in Europe and Africa.
If the first volunteers vaccinated in the Oxford study show a good response with no adverse reactions, the trial will, after approval from the relevant authorities, be extended to volunteers at the MRC Unit in The Gambia. A second West African arm of the study, led by Professor Myron M Levine of the Center for Vaccine Development at the University of Maryland School of Medicine, and Professor Samba Sow of the Center for Vaccine Development in Mali (a joint initiative between the University of Maryland School of Medicine and the Ministry of Health of Mali), will then begin in Bamako, Mali.
The Oxford study will involve 60 healthy volunteers, while those in The Gambia and Mali will each involve 40. Each set of volunteers will be split into groups of 20 that will receive different doses of the vaccine so researchers can evaluate the best dose to use in terms of both safety and activity.
NIAID are testing this same vaccine in the USA, in addition to a related vaccine that is designed to protect against two Ebola species (Ebola Zaire and Ebola Sudan).
This collaborative multi-trial approach will help ensure the fastest possible progress to determining the best candidate vaccine approach and delivery. The addition of west African arms will also ensure that the studies take account of differences between European and west African populations that might affect safety or immune response.
It is hoped that the phase 1 trials might be finished by the end of 2014, after which deployment of the vaccine could be fast-tracked should it prove to be safe and immunogenic.
Dr Moncef Slaoui, Chairman of Global R&D and Vaccines at GSK said: "Today's announcement shows how private and public partners can pull together to respond to this critical public health emergency. Developing a new vaccine is complex with no guarantees of success and it's still early days for our Ebola vaccine candidate. But we are encouraged by progress so far and will do the best we can, along with WHO and our partners, to speed up development and explore ways in which the vaccine could contribute to the control of this or future Ebola outbreaks."
Professor Adrian Hill, Director of the Jenner Institute at the University of Oxford said: "The tragic events unfolding in Africa demand an urgent response. In recent years, similar investigational vaccines have safely immunised infants and adults against a range of diseases including malaria, HIV and Hepatitis C. We, and all our partners on this project, are optimistic that this candidate vaccine may prove useful against Ebola."
Dr Jeremy Farrar, Director of the Wellcome Trust, said: "This epidemic has shown how difficult it can be to control Ebola. How useful drugs and vaccines might be in complementing existing public health interventions can only be assessed in epidemics. The initial safety work we're announcing today with our international partners will hopefully make that possible during this crisis and for inevitable future epidemics."
Professor Umberto D'Alessandro, Director of MRC Unit, The Gambia, said: "Thanks to the long-term collaboration between the UK’s MRC and the Gambian Government's Ministry of Health, we have the proven capacity and expertise to carry out trials to the highest quality standards including trials for vaccines similar to this one. The proposed trial won’t benefit immediately those currently at risk but we hope that in a not too distant future we may be able to protect people against Ebola."
Professor Myron Levine, Director of the University of Maryland School of Medicine Center for Vaccine Development, said: "This is an extraordinary effort of multiple groups working together to bring a promising early stage candidate Ebola vaccine to field tests in west Africa in record time. On short notice, the project partners have contributed enormous energy, time and resources to respond to the Ebola disease calamity. If the vaccine trials begin according to schedule, a new paradigm will have been established whereby multiple agencies mobilize to address a public health threat by accelerating the preliminary evaluation of a promising potential public health tool."
International Development Secretary, Justine Greening said: "We are co-funding these important clinical trials to find a safe vaccine for Ebola as well as providing critical care on the ground. Britain is a world leader in medical research and mobilising our unique strengths to find a vaccine could be pivotal to containing Ebola and preventing future outbreaks."
The NIAID/GSK Ebola vaccine candidate is based on an attenuated strain of chimpanzee cold virus, called chimp adenovirus type 3 (ChAd3). The adenovirus is used as a carrier, or vector, to deliver benign genetic material derived from the Ebola virus Zaire species that has caused the current Ebola outbreak in west Africa. The genetic material contained in the investigational vaccine cannot cause a vaccinated individual to become infected with Ebola. The vaccine candidate delivers the Ebola genetic material to human cells but does not replicate further. Rather, it allows the vaccine recipient's cells to express a protein, and that protein prompts an immune response in the individual.
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The Medical Research Council Unit in The Gambia is the UK's single largest investment in medical research in a developing country, and is internationally recognised for its track record of research into tropical infectious diseases. Its success is based on innovative lab-based research, excellent clinical studies and field-oriented science, and the translation of research into clinical and public health practice. The Unit’s vision is to lead scientific research to save lives and improve health across the developing world. It aims to deliver this through investment in four major research themes: Child Survival, Vaccinology, Disease Control and Elimination, and most recently Nutrition, following the integration of the International Nutrition Group into the Unit to further enhance investigations of the important role of nutrition in each of the research themes.
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