Ebola Vaccine Programme

Felicity Hartnell and volunteer
Clinical trial physician Felicity Hartnell administers the Jenner Institute's Ebola vaccine 'MVA ZEBOV GP' to the first volunteer in Oxford.

In August 2014, the World Health Organisation (WHO) declared the current Ebola outbreak in West Africa a “public health emergency of international concern”. Following consultation with scientists, the WHO moved to fast-track clinical trials of available candidate Ebola vaccines through an international consortium including the MRC, Wellcome Trust and the UK Department for International Development. Four of these vaccines have been tested in clinical trials at the Jenner Institute and Department of Paediatrics at Oxford University, in collaboration with vaccine manufacturers including GSK, Jansenn, Bavarian Nordic and Emergent Biosolutions.             

Research Aims

The Ebola vaccine research program has two key aims:

1. To facilitate clinical evaluation of candidate Ebola vaccines in human clinical trials so that exisitng vaccine candidates can be evaluated for their usefulness in outbreak control.

2. To develop new vaccine candidates that build on the knowledge we have gained both from the 2014-2016 outbreak in West Africa and our previous clinical trials data to improve on existing vaccines.

Many of the vaccines we develop at the Jenner Institute use a chimpanzee adenovirus to stimulate an immune response in the vaccinated volunteer, in the case of Ebola the immune response is against the glycoprotein from the Zaire strain of Ebola, which was responsible for the recent outbreak. Adenoviruses from chimpanzees have been used successfully to produce protective immunity against malaria and are safe for use in humans.  A single gene from the Ebola virus is transferred into the genetic material of the adenovirus vector using DNA technology. When administered to a volunteer, the adenovirus produces the protein from the gene along with its own proteins. The human immune system responds to the protein making immune cells and antibodies against the Ebola virus. If the person then encounters the real Ebola virus, the immune system will recognise that single protein and the immune cells and antibodies will destroy the infection before the person becomes ill.

We have recruited over 150 healthy volunteers for our Phase I clinical trials in Oxford to evaluate safety and immunogenicity. We have also undertaken a Phase I trial in Senegal to evaluate vaccines in healthy Senegalese adults. Many of the volunteers in these studies were vaccinated in 2014-15 and we continue to monitor their immune responses to understand how long the immunity produced by these vaccines can persist.

Our trials are based at the Oxford Vaccine Centre at the Churchill Hospital.

Publications:

  1. Chimpanzee adenoviral vectors as vaccines for outbreak pathogens. Ewer K, Sebastian S, Spencer AJ, Gilbert S, Hill AVS, Lambe T. Hum Vaccin Immunother. 2017 Dec 2;13(12):3020-3032. doi: 10.1080/21645515.2017.1383575. PMID:29083948
  2. A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? Lambe T, Bowyer G, Ewer KJ. Philos Trans R Soc Lond B Biol Sci. 2017 May 26;372(1721). doi: 10.1098/rstb.2016.0295. PMID:28396468

  3. Vaccines against Ebola virus. Venkatraman N, Silman D, Folegatti PM, Hill AVS. Vaccine. 2017 Aug 2. pii: S0264-410X(17)30962-3. doi: 10.1016/j.vaccine.2017.07.054. PMID:28780120

  4. A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA. Ewer K, Rampling T, Venkatraman N, et al. N Engl J Med. 2016 Apr 28;374(17):1635-46. doi: 10.1056/NEJMoa1411627. PMID:25629663
  5. Viral vectors as vaccine platforms: from immunogenicity to impact. Ewer KJ, Lambe T, Rollier CS, Spencer AJ, Hill AV, Dorrell L. Curr Opin Immunol. 2016 Aug;41:47-54. doi:10.1016/j.coi.2016.05.014. Epub 2016 Jun 7. PMID:27286566

  6. Safety and Immunogenicity of Novel Adenovirus Type 26- and Modified Vaccinia Ankara-Vectored Ebola Vaccines: A Randomized Clinical Trial. Milligan ID, et al. JAMA. 2016 Apr 19;315(15):1610-23. doi: 10.1001/jama.2016.4218. PMID:27092831

  7. Detection of Vaccine-Induced Antibodies to Ebola Virus in Oral Fluid. Lambe T, et al,. Open Forum Infect Dis. 2016 Feb 22;3(1):ofw031. doi: 10.1093/ofid/ofw031. eCollection 2016 Jan. PMID:27004234

  8. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial Tapia MD, et al., Lancet Infect Dis. 2016 Jan;16(1):31-42. doi: 10.1016/S1473-3099(15)00362-X. PMID:26546548