Ebola+

Ebola and other filoviral haemorrhagic fevers
Ongoing | IMI1 |

Summary

The IMI Ebola+ programme was launched in response to the Ebola virus disease (EVD) outbreak that started in western Africa in 2014. The comprehensive programme contributes to efforts to tackle a wide range of challenges in Ebola research, including vaccines development, clinical trials, storage and transport, as well as diagnostics and treatments. It is hoped that the programme, which complements work being carried out with the support of other funding bodies, will help to make a difference in the current and future outbreaks. In addition to Ebola, the programme will also address related diseases, such as Marburg. Eight projects, with a total budget of over €200 million, were selected for funding under the first Ebola+ Call for proposals. A second open Call on Ebola and related diseases was launched in December 2015.

Vaccine development

There are currently no licensed vaccines for Ebola. However, there are a number of vaccine candidates in development, and three projects in the new IMI Ebola+ programme will generate 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.

VSV-EBOVAC

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.

EBOVAC 1 and 2

Between them, the two EBOVAC projects will assess, 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 will be carried out by the EBOVAC1 project. These trials will gather preliminary information on the safety and tolerability of the vaccine regimen. The immune response generated by the regimen will also be 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.

Vaccine manufacture capability

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.

EBOMAN

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.

Deployment of and compliance with vaccination regimens

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.

EBODAC

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.

Rapid diagnostic tests

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.

Mofina

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.

FILODIAG

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.

EbolaMoDRAD

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.

IMI Open Call on Ebola and related diseases

In December 2015, IMI launched a two year, €70 million open Call for proposals (IMI 2 - Call 8) that invites consortia to submit proposals covering diverse aspects of Ebola research, including the development of vaccines, diagnostic tests, and treatments. The resulting projects should be able to capture emerging scientific advances and turn them into healthcare interventions that will increase our readiness to react to future outbreaks of Ebola or related diseases. The Call has a total budget of €70 million and will remain open for a period of two years with the following cut-off dates for submission of proposals: 16 March 2016, 15 September 2016, 16 March 2017, 14 September 2017, 15 March 2018. The €70 million budget from IMI will be available from the first cut-off date.

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 2014-15 Ebola epidemic is unprecedented in its scale and geographical distribution. By the end of 2014, World Health Organization (WHO) statistics recorded around 20 000 cases and 8 000 deaths from the disease, most of them in Guinea, Liberia, and Sierra Leone.

Achievements & News

EBOVAC2 clinical trials underway in France
IMI Ebola project EBOVAC2 has launched a campaign in France to recruit around 300 volunteers for a trial Ebola vaccine regimen. The goal of this study is to assess the safety and efficacy of a novel prime boost preventive regimen against Ebola virus disease. ### The vaccine regimen under investigation has two parts – a ‘prime’ vaccine to stimulate the immune system and a ‘boost’ vaccine to strengthen and extend the immune response. Additional volunteers are being recruited in the UK and in Africa. ‘Participants in this trial cannot become infected with the Ebola virus, said EBOVAC2 project coordinator Rodolphe Thiébaut of INSERM. ‘Only synthetic proteins or parts of proteins are used in the various vaccines being tested. They cannot in any way cause infection. This is based on the same principle as many existing vaccines for infectious diseases.’
- Read the INSERM press release on EBOVAC2 (January 2016)

EBOVAC trial in Sierra Leone starts; boosts local health infrastructure
A clinical trial of an investigational Ebola vaccine regimen is now underway in Kambia, Sierra Leone thanks to the IMI projects EBOVAC1, EBODAC and EBOMAN. ###Even in the short term, the benefits to the local community of the ‘EBOVAC-Salone’ trial are immense; new facilities had to be built to run the study, including the first emergency room at the local district hospital, and a vaccine storage facility. In addition, the project provides both jobs and training for local healthcare workers, who will also gain valuable experience by working on the trial. In the longer term, the community may also benefit if the vaccine regimen is approved. Sierra Leone was at the epicentre of the Ebola outbreak, with 14 000 cases and 4 000 deaths, including many healthcare workers.  The vaccine regimen under investigation is a ‘prime-boost’ regimen, in which two doses are given several weeks apart. The first dose ‘primes’ the immune system, while the second ‘boost’ reinforces its effects with the goal of potentially strengthening and optimising the duration of the immunity.  The study is notable in that it will evaluate the vaccine regimen’s safety and immune response within the general population of Sierra Leone, including vulnerable groups such as adolescents and children. The vaccine regimen is also in trials in other parts of Africa, Europe and the US. The EBOVAC-Salone trial is working closely with the IMI project EBODAC, which aims to ensure the prime-boost vaccine regimen is well accepted and successfully deployed. It is doing this by informing local engagement strategies, designing graphical communication aids, deploying technological solutions to increase compliance and uniquely identifying trial participants.
(October 2015)

Giant steps forward in Ebola vaccine quest, but research must continue
Earlier this summer, researchers announced in The Lancet that an Ebola vaccine developed with Merck had shown 100% effectiveness in a Phase III clinical trial of over 7 000 people in Guinea. This is one of the potential vaccines being developed for the disease, and researchers say that work must continue. ###IMI’s VSV-EBOVAC project in detail the signatures of immune responses elicited in humans by the VSV-ZEBOV vaccine using cutting-edge technologies combining in-depth human immune, transcriptomics and metabolomics profiling in relation to safety and immunogenicity. One of the outstanding questions – which VSV-EBOVAC hopes to answer once enough time has elapsed since the Phase I trial, started in November 2014 – is how long the immunisation remains effective. Many believe that the Merck vaccine should be used to protect those at high risk in areas still affected by Ebola. However, it may take months for approval by authorities. The timing means that these vaccines under development are unlikely to have much of an impact on the current epidemic. However, these vaccines have been developed at unprecedented speed, and the work being done lays down techniques that could be used in similar fast-moving epidemics. To find out more, read the Horizon Magazine article
(September 2015)

IMI-supported Ebola vaccine trials get underway in Africa
clinical trial of an Ebola vaccine regimen run through the IMI project EBOVAC1 has started in Kenya and Uganda. The trials are Phase I studies designed to evaluate the safety of the vaccine regimen and evaluate the long-term immune response to a regimen developed at the Janssen Pharmaceutical Companies of Johnson and Johnson. ###In each of the Phase I trial sites, 36 healthy adult volunteers receive either a placebo, or a two-part ‘prime-boost’ vaccine regimen, comprising an initial dose to prime the immune system and a ‘boost’ to enhance the immune response in the longer term. Similar studies are already underway in the UK and US and further studies in Africa, including in Sierra Leone, are anticipated to receive approval soon. The EBOVAC1 project is part of IMI’s wider Ebola+ programme, which currently covers vaccines and diagnostics and it is hoped will deliver results that will contribute to efforts to tackle both the current and future outbreaks. According to WHO reports, as of mid-April there had been over 25 000 confirmed, probable, and suspected cases of Ebola in the current outbreak and over 10 000 deaths, most of them in Guinea, Liberia, and Sierra Leone. (April 2015)

First IMI Ebola projects get underway
The Innovative Medicines Initiative (IMI) is launching the first eight projects of its Ebola+ programme, to accelerate all aspects of vaccine development and manufacturing as well as deployment and compliance with vaccine regimens and diagnostics. The eight projects were selected from proposals submitted under IMI’s first Ebola+ Call for proposals, which was launched in November 2014. ###The projects will have a total budget of €215 million, part of which comes from Horizon 2020, the EU’s research and innovation programme, and part of which comes in the form of in-kind contributions from the European Federation of Pharmaceutical Industries and Associations (EFPIA) partners in the projects. Of the eight projects, three will focus on the development of Ebola vaccines; one will work on scaling up vaccine manufacture; one will develop strategies to promote compliance with vaccine regimens; and three aim to develop rapid diagnostic tests that can be used at the point of care and at major infrastructures like airports.
-Read the IMI press release
(January 2015)

Innovative Medicines Initiative launches Ebola+ programme
The Innovative Medicines Initiative (IMI) is launching a multi-million euro programme on Ebola and related diseases such as Marburg haemorrhagic fever. Dubbed Ebola+, the comprehensive programme will see pharmaceutical companies collaborating with each other and with experts from universities, small biotech companies, regulators, and others to tackle a broad range of challenges in Ebola research. ### The first Call for proposals in the programme has a total budget of €280 million and will result in projects addressing the development, manufacture, transport, and storage of vaccines; ensuring compliance with vaccine regimens; and the development of rapid diagnostic tests. The first projects are expected to begin in early 2015, and the hope is that they will deliver results that will contribute to tackling both the current and future outbreaks.
- Read the IMI press release
(November 2014)

Participants

Details of all project participants can be found on the individual project factsheets.

CONTACT

Contact details for the projects can be found in the individual project factsheets.