Periodic Reporting for period 7 - EBOVAC1 (Development of a Prophylactic Ebola Vaccine Using an Heterologous Prime-Boost Regimen – Sofia ref.: 115854)
Periodo di rendicontazione: 2021-01-01 al 2021-11-30
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 was responsible for conducting clinical trials in Europe and Africa to assess the safety, tolerability and immunogenicity (immune response) of the two-dose vaccination regimen using the vaccines Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) developed by Janssen Vaccines & Prevention B.V. part of the Janssen Pharmaceutical Companies of Johnson & Johnson, in collaboration with Bavarian Nordic. 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 boosting the immune response and extending the duration of immunity.
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 was responsible for conducting clinical trials in Europe and Africa to assess the safety, tolerability and immunogenicity (immune response) of the two-dose vaccination regimen using the vaccines Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) developed by Janssen Vaccines & Prevention B.V. part of the Janssen Pharmaceutical Companies of Johnson & Johnson, in collaboration with Bavarian Nordic. 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 boosting the immune response and extending the duration of immunity.
EBOVAC1 implemented and completed three Phase 1 clinical trials in the UK, Kenya, and Uganda/Tanzania, in which a total of 231 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 July 2019. A total of 1,019 participants were enrolled into this study, comprising 443 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 397 adults, 145 adolescents aged 12-17, 117 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). 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 for at least 1 year after vaccination.
The results from the Phase 1 trials 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 3 study in Sierra Leone (EBL3001) were presented in two articles published in September 2021 in the Lancet Infectious Diseases (https://doi.org/10.1016/ S1473-3099(21)00125-0 and https://doi.org/10.1016/ S1473-3099(21)00128-6). These data confirmed the findings of previous studies, again demonstrating that the vaccine regimen was well tolerated and produced durable immune responses in adults and children.
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 397 adults, 145 adolescents aged 12-17, 117 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). 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 for at least 1 year after vaccination.
The results from the Phase 1 trials 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 3 study in Sierra Leone (EBL3001) were presented in two articles published in September 2021 in the Lancet Infectious Diseases (https://doi.org/10.1016/ S1473-3099(21)00125-0 and https://doi.org/10.1016/ S1473-3099(21)00128-6). These data confirmed the findings of previous studies, again demonstrating that the vaccine regimen was well tolerated and produced durable immune responses in adults and children.
The ongoing risk to global public health posed by the Ebola virus is clear. During 2020, two separate outbreaks were declared over in different parts of the Democratic Republic of the Congo (DRC). A new case of Ebola Virus Disease was reported in the eastern DRC as well as a further outbreak in Guinea in February 2021.
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 aimed to provide the data to establish the safety and immunogenicity of a novel two-dose vaccination regimen, and these data are now available.
On 1st July 2020 the European Medicines Agency (EMA) granted a marketing authorisation for use of the 2-dose Ebola vaccine regimen Ad26.ZEBOV MVA-BN-Filo in the European Union in adults and children above one year of age. In April 2021, the vaccine regimen was also granted WHO Prequalification, which will facilitate formal registrations of this vaccine regimen in countries at risk of Ebola virus disease outbreaks. Janssen is also pursuing a biologics license application (BLA) filing with the U.S. Food and Drug Administration (FDA).
It is hoped that the Janssen vaccine regimen will be recommended by regulatory bodies 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 Janssen vaccine regimen may be used in the future.
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 to 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.
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 aimed to provide the data to establish the safety and immunogenicity of a novel two-dose vaccination regimen, and these data are now available.
On 1st July 2020 the European Medicines Agency (EMA) granted a marketing authorisation for use of the 2-dose Ebola vaccine regimen Ad26.ZEBOV MVA-BN-Filo in the European Union in adults and children above one year of age. In April 2021, the vaccine regimen was also granted WHO Prequalification, which will facilitate formal registrations of this vaccine regimen in countries at risk of Ebola virus disease outbreaks. Janssen is also pursuing a biologics license application (BLA) filing with the U.S. Food and Drug Administration (FDA).
It is hoped that the Janssen vaccine regimen will be recommended by regulatory bodies 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 Janssen vaccine regimen may be used in the future.
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 to 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.