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Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen: Phase II - Sofia ref.: 115861

Periodic Reporting for period 5 - EBOVAC2 (Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen: Phase II - Sofia ref.: 115861)

Reporting period: 2019-01-01 to 2019-12-31

Combining the expertise and capabilities of global research institutions, non-government organizations and the pharmaceutical industry has been critical to help address the Ebola public health challenge.

The Ebola vaccine projects - EBOVAC1, EBOVAC2, EBOVAC3, EBODAC and EBOMAN - are a series of clinical trials and associated projects which aim to assess a novel two-dose preventive vaccination regimen against Ebola Virus Disease (EVD). These projects are part of the IMI Ebola+ programme that was launched in response to the Ebola virus disease (EVD) outbreak that started in western Africa in 2014. The comprehensive programme includes 12 projects and contributes to efforts to tackle a wide range of challenges in Ebola research, including vaccines development, clinical trials, storage and transport, and diagnostics.

EBOVAC2 is responsible for conducting Phase 2 clinical trials in Europe and Africa to assess the safety, tolerability and immunogenicity (immune response) of the two-dose vaccination regimen (Ad26.ZEBOV and MVA-BN-Filo) in development by Janssen Vaccines & Prevention B.V. part of the Janssen Pharmaceutical Companies of Johnson & Johnson. The vaccine regimen involves an initial dose that stimulates the immune system to develop disease-specific antibodies, followed by a second dose two months later with the goal of potentially strengthening and optimizing the duration of immunity.

EBOVAC2 will complete this Phase 2 clinical work as well as some exploratory research aimed at better understanding the immune response to the vaccine and its underlying mechanisms.
EBOVAC2 has implemented two phase 2 trials in clinical sites in Europe and Africa. The Phase 2 trials were planned to start as soon as preliminary safety data from the EBOVAC1 Phase 1 trials in the UK and Africa became available. Sites in the UK, France and Africa started enrolment in 2015.

In 2016, the Phase 2 trial in the EU progressed well and enrolment was completed. EBL2002 study was conducted at Kenya, Uganda, Cote d'Ivoire and Burkina Faso. End of 2016, enrolment of healthy adults was nearly complete and the team prepared to open enrolment of HIV+ adults and children in 2017. Also in 2016, the results of the early response to the vaccine regimen became available in a subset of participants in the European trial (Cohort 1, UK). To extend the observations gained from phase 1 and 2 studies, EBOVAC2 developed a plan to facilitate a link between all projects from the IMI Ebola+ programme to contribute to better preparedness in case of future Ebola outbreaks. The consortium also contributed to the Central Information Repository that hosts information assets and project documentation from IMI Ebola+ projects.

In 2017 and 2018, the work proceeded as planned, finalising the enrolment of volunteers, performing sophisticated immunologic analyses and preparing clinical data for use in regulatory documents. In 2018, only Cohort 3 (children ages 4-11 years) and the 90 volunteers who agreed to participate in the booster dose sub-study were still in the final follow-up stage in Africa. For all other cohorts volunteers had entered the long-term safety extension study (outside the scope of EBOVAC2). Preliminary safety and core immunogenicity results of both Phase 2 studies became available and were presented to the European and African Principal Investigators at the end of 2018. A workshop on vaccine clinical trial methodology was successfully organized in Burkina Faso for West African young medical researchers in January 2018.

In 2019, EBOVAC2 was amended following our second project review to allow the partners to finalize and publish the clinical trials results within project timelines and complete the exploratory analysis work according to the reviewers' recommendations. The clinical work at the sites has been finalized. The focus turned towards preparing regulatory documents, clinical study reports and publications for EBL2001 and EBL2002. The results of the core analysis were presented at the IMI Annual Meeting in Nairobi. The exploratory work was continued in 2019 notably on the cellular response to vaccination in B cell and NK cell principally). Data centralization allowed for the integrative statistical analyses to be performed to further develop mathematical models of infectious diseases to gain understanding of complex systems and provide a framework for making predictions and projections under different scenarios.

In 2020, EBOVAC2 will finalize the remaining exploratory work and complete the publications of the core trials and the immune response research. EBOVAC2 plans to organize a final meeting at the end of this last period with a specific Stakeholder Day to further present the results obtained to a panel of key opinion leaders involved in the development of Ebola vaccines in Europe, the USA and in Africa. This will be the occasion to share the lessons learned from EBOVAC1, EBOVAC2, EBOVAC3, EBODAC and EBOMAN and contribute to global strategies to respond to the challenges brought not only by Ebola, but also by other emerging diseases.
The risk to global public health posed by the Ebola virus was reinforced in 2018, when the Democratic Republic of the Congo (DRC) experienced two unrelated outbreaks of the disease. The second outbreak, which began in August 2018 only days after the first was declared over and has continued into 2019, is now the second biggest recorded outbreak of Ebola.

Such a significant threat requires a long-term commitment, including implementation of surveillance systems, rapid response preparedness and the development and availability of effective vaccines. EBOVAC2 aims to provide the data to establish the safety and immunogenicity of a novel 2-dose vaccine regimen.

On 6 November 2019 Janssen submitted two MAAs to EMA for the 2-dose Ebola vaccine regimen Ad26.ZEBOV MVA-BN-Filo (one for each vaccine). EMA granted accelerated review (September 2019). Discussions for a biologics license application (BLA) filing for the Janssen vaccine regimen are ongoing with the U.S. Food and Drug Administration (FDA). Janssen is also applying for World Health Organization (WHO) Prequalification (PQ) for the Ebola vaccine regimen and is collaborating with the WHO to enable registration of the Ebola vaccine regimen in African countries. Rwanda granted the vaccine regimen conditional approval under exceptional emergency in September 2019.

If the vaccine regimen is found to be safe and immunogenic, it may be possible for it to be licensed for use as a preventive immunization strategy for health care workers and the general population in countries at risk of future outbreaks of EVD.

The economic costs of the last epidemic in West Africa were very high in the affected countries, but also in Europe where measures had to be taken to prevent importation of cases and to support the affected countries in Africa. The development of an effective Ebola vaccine which provides sustained protection could have financial benefits for the people of Europe as well as those living in countries at risk of future outbreaks of EVD (UN Development Group, 2015).

Finally, the lessons learned from this project will have a positive impact on global strategies to develop vaccines quickly in situations of public health emergencies, thereby helping to improve the world's preparedness for emerging infectious diseases.
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