- Vaccine development projects
- EBOVAC 1, 2 and 3
- Vaccine manufacture capability projects
- Deployment of and compliance with vaccination regimens projects
- Rapid diagnostic test projects
- About Ebola and related diseases
There are currently no licensed vaccines for Ebola. However, there are a number of vaccine candidates in development, and a number of projects in the IMI Ebola+ programme are generating the data needed to assess the safety and immunogenicity of different vaccine candidates and the level and duration of protection they actually offer against the disease.
EBOVAC 1, 2 and 3
The EBOVAC projects are assessing, through clinical trials in Europe and Africa, the safety and tolerability of the ‘prime-boost’ Ebola vaccine regimen (Ad26.ZEBOV and MVA-BN-Filo) in development at the Janssen Pharmaceutical Companies of Johnson & Johnson. In a prime-boost vaccine regimen, patients are first given a dose to prime the immune system, and then a boost dose which is intended to enhance the immune response over time.
Phase I trials are carried out by the EBOVAC1 project. These trials are gathering preliminary information on the safety and tolerability of the vaccine regimen. The immune response generated by the regimen is also being evaluated longer term.
Subject to review of the preliminary Phase I data, the Phase II and III trials, will be carried out in parallel by the EBOVAC2 and EBOVAC1 projects respectively to speed up the clinical development of the vaccine regimen. In these trials, larger groups of people will receive the vaccine regimen, allowing the projects to gather further information on the regimen’s safety and immunogenicity, including in specific groups such as children and the elderly, and to assess its efficacy against Ebola virus.
EBOVAC3, which was launched in 2018, builds on the work of EBOVAC1 and 2 and aims to run clinical trials in children in Sierra Leone, Guinea and the Democratic Republic of Congo. It will also follow up people who participated in earlier clinical trials in Sierra Leone, to assess the safety and efficacy of the vaccine in the longer term.
VSV-EBOVAC will build on existing work to advance the development of the Ebola vaccine candidate VSV-ZEBOV (‘vesicular stomatitis virus-vectored Zaire Ebola vaccine’). The World Health Organization (WHO) has identified VSV-ZEBOV as one of the most promising Ebola vaccine candidates, and clinical trials are already underway in Europe and Africa. The VSV-EBOVAC project will use cutting-edge technologies to carry out in-depth analyses of samples taken from clinical trial participants before and after vaccination. This will allow them to gather vital information on both the strength of the immune responses triggered by the vaccine and vaccine safety.
The VSV-EBOPLUS project aims to use systems biology approaches to decipher the molecular and immune signatures of responses to the vaccine in both adults and children in the short and long term. To do this, they will study blood samples taken from different groups, including adults and children who have just received the vaccine. They will also carry out yearly follow-up visits with two of the largest cohorts, in Gabon and Switzerland, for five years following vaccination. The project hopes that the results will deliver novel insights into the mechanisms of action of VSV-ZEBOV, and provide signatures that can be used to accurately assess both the safety and effectiveness of vaccines.
Although there are promising Ebola vaccines in development, their large-scale deployment could be limited by issues such as the fact that they need to be stored at extremely low temperatures (-80°C). PEVIA aims to develop second generation Ebola vaccines based on the proteins found on the surface of the virus. The project hopes that the resulting regimen will be better suited to large-scale vaccination programmes in sub-Saharan countries, most notably because it will not require storage at low temperatures. In addition, PEVIA aims to develop innovative tools and methods to facilitate the development of new vaccine candidates for Ebola and related diseases, as well as novel diagnostic tests that can be deployed in the field.
Ebola vaccines can only be manufactured in facilities with an appropriate biosafety rating. Relatively few manufacturers have the biosafety rating required for the manufacture of Ebola vaccines, and this is slowing down the production of vaccine candidates.
The focus of the EBOMAN project is on accelerating the development and manufacturing of a ‘prime-boost’ Ebola vaccine regimen (Ad26.ZEBOV and MVA-BN-Filo) in development at the Janssen Pharmaceutical Companies of Johnson & Johnson. In the short term, this will ensure the delivery of sufficient quantities of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen to support the EBOVAC projects to perform the clinical trials. In parallel, this project will create additional vaccine production capacity to allow for the rapid preparation of large quantities of vaccines.
For a vaccine to have a real impact on an outbreak, high levels of vaccination coverage are essential. In addition, for lasting protection, two doses of the vaccine may be needed. However, the stigma surrounding Ebola, coupled with a suspicion of vaccines in general, could deter many people from getting vaccinated. Strong communication campaigns are therefore needed to address these challenges.
The EBODAC project will develop a communication strategy and tools to promote the acceptance and uptake of new Ebola vaccines. One of the project’s most important products will be a platform, based on mobile technology, dedicated to Ebola vaccines. As well as providing local communities with information on Ebola and vaccines, the platform will send reminders to people receiving the ‘prime boost’ vaccine to return to get their second ‘booster’ dose and facilitate the tracking of vaccination coverage. EBODAC will also set up local training programmes to make sure the communication strategy, and its tools, will be ready for deployment in the local setting.
There is an urgent need for fast, reliable tests to determine if someone is infected with Ebola or not. Three projects will pave the way for rapid diagnostic tests capable of delivering reliable results at the point of care in as little as 15 minutes.
The Mofina project will develop a new diagnostic test that will deliver results in under 45 minutes on whether the patient has Ebola or a related disease such as Marburg virus. Crucially, the device is designed to work well in sites where high-end laboratory infrastructures are simply not available, while also protecting users from infection. The project will draw on two existing technologies: a conventional Ebola virus test, and a point-of-care molecular diagnostics platform. After testing a prototype of the system, the project partners will validate it in the field.
The FILODIAG project aims to deliver an ultra-fast, accurate diagnostic instrument that will test for Ebola in under 15 minutes. Such a system could be used in both healthcare settings and at critical infrastructures like airports. Current tests for Ebola virus take a long time because samples must be heated and then cooled in each of the many processing cycles. This project will replace the heating/cooling steps with a technology based on laser-heated nanoparticles. Early tests of this technology have worked well. The project will add a step to concentrate the virus and refine and test the system before evaluating it in the field.
The EbolaMoDRAD project aims to develop and validate in the field a rapid diagnostic tool that will be both simple and safe to use in low resource settings by people who may not have specialist training. At the same time, the project will implement a large-scale capacity building programme in West Africa with a strong focus on diagnostics, biosafety, and outbreak management. Finally, it will ensure its results are communicated widely, especially to public health bodies, charities, outbreak management teams, and local hospitals.
VHFMoDRAD builds on the work of EbolaMoDRAD and as such aims to develop rapid point-of-care (POC) diagnostic tools capable of identifying a number of viral haemorrhagic fevers. The new tools and methods developed by VHFMoDRAD will be validated in the field. In addition, the project plans to run training courses for professionals in the west African region. It will also transfer the production capacity for the diagnostic tools to a project partner in the region so that the tests can be produced locally. Ultimately, VHFMoDRAD will contribute to better preparedness for outbreaks of viral haemorrhagic fevers, and to capacity building in Africa.
About Ebola and related diseases
Ebola virus disease (EVD), previously known as Ebola haemorrhagic fever, is a rare and deadly disease caused by infection with one of the Ebola virus strains. The virus spreads in the human population through direct human-to-human contact with the bodily fluids of infected patients who are showing symptoms. It has an incubation period of 2-21 days, and it usually begins with flu-like symptoms, but rapidly progresses to multiple organ failure and blood-clotting abnormalities which manifest as internal and external haemorrhages (bleeding). It is fatal in between 25% and 90% of cases. There is currently no licensed treatment against EVD, and the development of treatments and preventive measures such as vaccines is hampered by challenges including manufacturing-related hurdles, the stability of vaccines during transport and storage, vaccine deployment, and the time taken to diagnose cases of EVD.
Ebola is a member of the filovirus family of viruses, which also includes Marburg virus. Like Ebola, Marburg causes cause severe, often fatal haemorrhagic fever in humans and other primates (monkeys, gorillas and chimpanzees), and like Ebola, it is transmitted directly from one person to another. (In contrast, other viruses that cause haemorrhagic fevers are spread via intermediate hosts - for example, dengue fever is transmitted by mosquitoes.) There is no specific treatment or vaccine against Marburg heamorrhagic fever.
The 2014-16 Ebola epidemic was unprecedented in its scale and geographical distribution. World Health Organization (WHO) statistics recorded over 28 000 cases and 11 000 deaths from the disease, most of them in Guinea, Liberia, and Sierra Leone.