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Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen – Sofia ref.: 115854

Periodic Reporting for period 5 - EBOVAC1 (Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen – Sofia ref.: 115854)

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

EBOVAC1 is one of the Ebola vaccine projects (EBOVAC1, EBOVAC2, EBOVAC3, EBODAC and EBOMAN), a series of clinical trials and associated projects which aim to assess a novel two-dose preventive vaccine regimen against Ebola Virus Disease (EVD).

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

The EBOVAC1 project is responsible for conducting 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.
EBOVAC1 has implemented and completed three Phase 1 clinical trials in the UK, Kenya, and Uganda/Tanzania, in which a total of 219 adults were enrolled. A staged Phase 2B clinical trial in Sierra Leone – known as EBOVAC-Salone – began in 2015, and the last participant visit was completed in June 2019. A total of 1,020 participants were enrolled into this study, comprising 444 adults, 192 adolescents aged 12-17, 192 children aged 4-11 and 192 children aged 1-3. This study was the first study to include toddler-age children following a successful age-de-escalation and review by an external safety monitoring board.

An additional Phase 2 study in Sierra Leone – known as SL PREVAC – to evaluate the safety and immunogenicity of three experimental Ebola vaccination strategies was also implemented by the EBOVAC1 team. A total of 708 participants were enrolled into the SL PREVAC study, comprising 399 adults, 145 adolescents aged 12-17, 115 children aged 5-11 and 49 children aged 1-4. The last participant visit in this study was completed in November 2019. SL PREVAC forms part of a larger study, with funding from NIAID, covering Guinea, Liberia and Mali.

Data from the EBOVAC1 studies overall indicate that the vaccine regimen is well tolerated and produces a strong and durable immune response in both adult and paediatric populations.

The Phase 1 trial results from the UK study (EBL1001) were published in JAMA: The Journal of the American Medical Association in April 2016 (http://dx.doi.org/10.1001/jama.2016.4218). In the UK study, the two-dose vaccination regimen was well-tolerated and immunogenic (produced an immune response). Final data from the same study published in JAMA in March 2017 (http://dx.doi.org/10.1001/jama.2016.20644) showed that the immune response persisted in volunteers at 1 year post-vaccination. The Phase 1 trial results from the studies in Kenya (EBL1003) and Uganda/Tanzania (EBL1004) were published in the Journal of Infectious Diseases in February 2019 (https://doi.org/10.1093/infdis/jiy625 and https://doi.org/10.1093/infdis/jiz070). In both studies, the data show that the vaccine regimen was well tolerated and highly immunogenic.

Data from the Phase 2B study in Sierra Leone (EBL3001) were presented at the European Congress of Clinical Microbiology & Infectious Diseases in April 2019. These data confirmed the findings of previous studies, again demonstrating that the vaccine regimen was well tolerated and produced durable immune responses in adult participants. The first data in children and adolescents from the EBL3001 study were combined with data from EBOVAC2’s EBL2002 study for presentation at the American Society of Tropical Medicine and Hygiene Annual Meeting in November 2019. Overall, the vaccine regimen was well tolerated and induced robust immune responses in healthy children aged 1 to 17 years which persisted up to one year.
The ongoing risk to global public health posed by the Ebola virus has been clear in 2019. The second biggest recorded outbreak of Ebola has plagued the eastern Democratic Republic of the Congo (DRC) throughout the year, and as a result the vaccine regimen being studied in EBOVAC1 is also now being made available through a new clinical study in the DRC and is also being provided in an immunisation programme in neighbouring Rwanda.

It is clear that the global public health community must continue the fight against 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.

EBOVAC1 aims to provide the data to establish the safety and immunogenicity of a novel two-dose vaccination regimen, and much of these data are now available.

In 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.

Janssen is in discussion with the World Health Organisation, the US FDA and the European Medicines Agency seeking licensure for the vaccine regimen, with the goal of licensing the vaccine regimen for use as a preventive immunisation strategy for health care workers and the general population in countries at risk of future outbreaks of EVD. Mathematical modelling work being undertaken by EBOVAC1 to compare different potential vaccination roll-out strategies can help to inform how best the vaccination regimen may be used in the future. One possible application being researched includes a preventive immunisation strategy for health care workers and the general population in countries at risk of future Ebola outbreaks.

The economic costs of the 2014-2016 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 also to provide support for 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).

A further potential impact of this project is the skill and infrastructure capacity building in affected countries for vaccine development and evaluation. The EBOVAC1 project contributed in building such capacities for clinical trials in Sierra Leone by training local staff as well as establishing a vaccine depot, a research laboratory, an emergency room, and improved paediatric facilities at the local district hospital (image 1).

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.
Emergency Room at the Kambia Government Hospital, Sierra Leone, established by EBOVAC1
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