As of June 2016, there have been a total of 28,616 reported confirmed, probable, and suspected cases of Ebola Virus Disease (EVD) in Guinea, Liberia and Sierra Leone, with 11,310 reported deaths (this total includes reported deaths among probable and suspected cases, although outcomes for many cases are unknown). For an update on the outbreak please visit the WHO Ebola virus disease outbreak.

WP 1: Project Management

The EbolaVac project reached its conclusion on April 6th 2018 and the second and final project report was submitted on time to the European Commission, in June 2018. During the last two years of the project the consortium worked very hard in order to complete all ongoing clinical trials, analyse all samples collected and perform data analysis

The results of the project have been presented at international congresses, meetings and workshops and were shared with different stakeholders such as governments and NGOs including WHO towards improved efforts to better prepare for recurring public health emergencies.

Download the Ebolavac summary for further details.

Final Meeting of the EbolaVac consortium:

The final EbolaVac consortium meeting was held at the University Foundation in Brussels on March 21st 2018. The central location at the core of the European Headquarter offered the ideal setting to gather the consortium one last time and look back on the project achievements.

During this one-day meeting, each partner was able to present the scientific data generated throughout the course of the project. During the afternoon session, time was dedicated to reflect upon project conclusions and results exploitation.

At the end of the meeting the three project independent advisors, Dr Vincent Ahonkhai, Dr Patricia Fast and Dr Sodiomon B Sirima, congratulated the consortium for their successful partnership and results achieved. They also encouraged the consortium to publish the lessons learnt from the project to benefit future preparedness in the event of other similar outbreaks.

Read more >>

WP 2: Phase ½ Lausanne Study

This trial was started on October 24th 2014 and was completed on June 22nd 2015. Between October 24th, 2014 and June 22nd, 2015 120 participants, 18 (15%) of whom were potentially deployed and 102 (85%) of whom were non-deployed, were randomly assigned to receive high dose vaccine, low dose vaccine, or placebo. All participants were followed up for 6 months post-treatment.

Safety, cellular and humoral immunity data were generated and analysed, and it was found that the two different doses of the ChAd3-EBO-Z candidate vaccine were both equally safe, well tolerated and able to induce comparable immune responses. These findings led to a publication (De Santis et al., 2016. Lancet Infect Dis) and, together with clinical data from other Phase 1 trials with the ChAd3-EBO-Z candidate, but which are not part of the Ebolavac project, they enabled the selection of the dose of ChAd3-EBO-Z to be used for subsequent Phase 2 trials (1x1011 vp dose selected).

Following completion of the clinical trial, the clinical study report was submitted and approved by the competent authorities. Final results were submitted to ClinicalTrials.gov by the sponsor in April 2018 (NCT02289027).

Read more >>

WP3: Phase 2 RCT in African Countries

Initial safety and immunogenicity data from Phase 1 studies of the ChAd3-EBO-Z candidate vaccine has enabled selection of the most appropriate dose for testing in subsequent clinical trial studies. A large safety/immunogenicity healthy-volunteer Phase 2 study in adults has started at the end of July 2015. Since data from the first 100 adults showed acceptable safety, a Phase 2 safety and immunogenicity study in healthy children was also started in November 2015.

For the Phase 2 adult study, GSK was able to recruit a total of 3032 subjects, aged 18 years and above, by December 2015. The study was completed on December 23rd, 2016. An interim analysis to assess safety, reactogenicity and immunogenicity data up to 30 days after vaccination was completed at the beginning of 2016 while final analysis was completed in the course of 2017. The final results were submitted to ClinicalTrials.gov by the sponsor in January 2018 (NCT02485301)

The Phase 2 paediatric study terminated the recruitment of its 600 subjects, subjects aged from 1 to 17 years in May 2016. An interim analysis based on data accrued during the 30-day period after vaccination was performed in the summer, 2016 while final analysis was completed in September 2017.

The results from final analysis were submitted to ClinicalTrials.gov by the sponsor in March 2018 (NCT02548078).

Main conclusions from the two trials are summarized below:

  • ChAd3-EBO-Z is well tolerated in subjects aged 1 year and above
  • ChAd3-EBO-Z induces persistent anti-GP EBOV ELISA antibody responses
  • ChAd3-EBO-Z induces ChAd3-EBOV CD4+ and CD8+ T cell responses in adults and children
  • ChAd3-EBO-Z induces ChAd3 neutralizing antibody responses in adults and children

Development of a publication is ongoing.

Read more >>

WP4: Booster Study and Immunology

The first vaccinations in the EBL06 clinical trial in Dakar, Senegal were administered on July 2nd 2015. Enrolment of the expected 40 volunteers in the trial was completed on July 14th 2015 and vaccinations were completed on July 21st 2015. The trial was completed early 2016.

Volunteers were followed up for safety and immunogenicity evaluations leading to an interim clinical study report completed in September 2015. The final clinical study report was finalized and submitted to the ethics committees in Senegal and the UK in 2017.

Main conclusions from the study are summarized below:

  • Following a priming vaccination with ChAd3-EBO-Z, MVA-GSK-EBO-Z was well tolerated in healthy Senegalese adult participants
  • Immunization with MVA-GSK-EBO-Z boosted the immunity induced by ChAd3-EBO-Z immunization, increasing titres of anti-GP EBOV ELISA antibody responses and CD4+ and CD8+ T cell responses

Development of a publication and posting of the results on the trial registry is ongoing.

Read more >>

WP6: Communication and Dissemination

The first EBOLAVAC paper was published in the Lancet Infectious Diseases journal in March 2016. In this publication titled “Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study”

the authors assessed the safety and immunogenicity of a single injection of 2 different doses of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z) by means of a clinical trial performed on healthy volunteers in Switzerland.

The trial demonstrated the two different doses of the ChAd3-EBO-Z candidate vaccine to be both equally immunogenic, safe and well tolerated.

To get access to the Lancet Infectious Diseases publication, follow the link here: http://www.sciencedirect.com/science/article/pii/S1473309915004867.

In addition to this publication, a review entitled “A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?” was developed by the University of Oxford and was published on the journal Philosophical Transactions of the Royals Society B (Biological Sciences) in May 2017. To access this review, follow the link here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394635/pdf/rstb20160295.pdf Additional manuscripts are currently under preparation in order to further disseminate the data generated in the context of the two Phase 2 GSK-sponsored trials (WP3 adult and paediatric studies) as well as in the context of the WP4 Booster Study conducted in Senegal and sponsored by the University of Oxford.

The consortium has also had the opportunity to further disseminate project data and be represented at several international congresses such as (list not exhaustive): The 9th European Congress on Tropical Medicine and International Health; The 18th Annual Conference on Vaccine Research; The World Vaccine Congress in October 2017 and the ASTMH 2017 congress in November 2017 (Presentation of interim (D30) data of the EBOLAZ CHAD3-004 “Safety/Immunogenicity of a Single Intramuscular Dose of the Investigational Recombinant Chimpanzee Adenovirus Type 3-Vectored Ebola Zaire Vaccine (ChAd3-EBO-Z) in Children in Africa: A Phase 2, Randomized, Controlled Study”, Tapia et al.)

Finally, the results of EbolaVac were also shared with governments and NGOs incl. WHO towards improved efforts to better prepare for recurring public health emergencies.

Read more >>

WP7: Advanced cell line process development

The process development and cGMP production of MVA-EBO Z on the AGE1.CR.pIX® cell line (ProBioGen) was completed in February 2015. The advantage of the new cell line is that up to a million doses can be produced annually.

GMP manufacture was performed at Emergent Biosolutions, Baltimore, US with funding support from Wellcome Trust and the EbolaVac project. About 40,000 doses have been manufactured with 10,000 doses presented in multi-dose vials.

Ethical and MHRA approval has been granted for the first use of this vaccine in humans in a clinical trial (EBL04) that commenced in the UK in June 2015. Subsequently, the vaccine was administered for the first time in African volunteers to boost a single dose of the ChAd3-EBO-Z during the EBL06 booster study (WP4), described above. Data from this trial will complement and extend current Phase I and II data available on the safety, reactogenicity and immunogenicity of the ChAd3-EBO-Z candidate vaccine.

The fact that the MVA-EBO Z was manufactured on a cell line, as opposed to chicken embryo fibroblasts (CEFs) could potentially allow larger scale manufacturing of MVA than is possible using CEFs. Considering that Ebola affects some of the world’s poorer countries and can spread rapidly, finding an affordable method to scale up the manufacturing of a candidate vaccine is key to delivering an effective response to an Ebola outbreak.

Read more >>