EBOLA Outbreak: Four vaccines assessed in Oxford in six months

by Dr Katie Ewer, Senior Immunologist, Jenner Institute 

Ebola victims















The Jenner Institute has been at the forefront of Ebola vaccine evaluation and development as part of the response to the outbreak in West Africa that began in 2014.

Although several promising vaccine candidates against Ebola Virus Disease (EVD) had been tested in animal, none had been tested and shown promise in any human trial prior to the outbreak. Once the WHO declared a Public Health Emergency of International Concern in August 2014, an international effort began to accelerate evaluation of existing vaccines.

The key goal was to assess whether any could be used to protect health care workers in West Africa on the front-line of the response and to contain the spread of infection in the wider populations of the three affected countries.

Phase I & II Clinical Trials: ChAd3 ZEBOV GP (GSK) and MVA BN Filo (Bavarian Nordic)

In collaboration with the National Institutes of Health (NIH) in the US and GSK Vaccines, the Jenner Institute commenced a Phase I clinical trial to evaluate two Ebola vaccines targeted at the outbreak strain, but which had never been administered to humans, in healthy volunteers in Oxford. Getting the trial off the ground as quickly as possible was a big challenge. This would usually take at least six months, but given the urgency of the situation it was possible to obtain regulatory and ethical approval in a fraction of that time.

The findings of the clinical trial were published in the New England Journal of Medicine in a Preliminary Report in January 2015, and a follow-up full report in April 2016. Although the current outbreak has subsided, trials of other new Ebola vaccines are continuing and the Jenner Institute is expanding its role to design and develop vaccines against other emerging pathogens such as Zika and Chikungunya, for which no vaccines yet exist.

A steep learning curve: Although the types of vaccines being tested in the clinical trials, viral vectors, were similar to those developed by the Jenner Institute previously, no-one had ever worked on Ebola before then, meaning a steep learning curve for everyone in the team. The laboratories in particular had to develop and adapt their assays in collaboration with collaborators with more Ebola experience. Another challenge was to provide high quality immunology data to organisations such as the WHO as quickly as possible to inform the ongoing management of the outbreak and decisions about potential vaccine deployments.

Phase I Clinical Trial: MVA ZEBOV GP (Jenner Institute, Oxford)

During the outbreak, the Jenner Institute also arranged for manufacture of a new Ebola vaccine, ‘MVA ZEBOV GP’, which uses a novel production method and this demonstrated just how quickly a new vaccine could be delivered in the face of an emerging outbreak. See below for the production time line of ‘MVA ZEBOV GP’. This vaccine was chosen to match precisely the outbreak strain of Ebola Virus and to maximize the magnitude of the immune response to that strain because the MVA vector was known to amplify both humoral and cellular immunity when used as a booster vaccine. But the potential need for very large numbers of doses led to the use of a cell line and novel biomanufacturing process for the first time. This work at Emergent Biosolutions in the USA, under contract to the University, was completed in record time and showed that the new process has many advantages over the traditional egg-based methods. Overall, the potential for applying this technology in the field of vaccines for emerging pathogens is very considerable, especially when the next outbreak is unknown and vaccines are needed quickly.

Despite being a “first-in-human” study, the Ebola vaccine candidate ‘MVA ZEBOV GP’ was produced, released and approved for use at the Jenner Institute’s clinical trials facilities in just over six months. As the vaccine was manufactured in a cell-line not previously used for human vaccines, the production required additional discussion with the UK regulator (MHRA) regarding suitable release assays:

Ebola vaccine development in Oxford

Phase I & II Clinical Trials: Ad26.ZEBOV/MVA-BN-Filo (Janssen/Crucell)

By Dr Matthew Snape, BRC Consultant in Paediatrics and Vaccinology, Oxford Vaccine Group, Jenner Investigator

As part of the international response to the recent Ebola disease outbreak, the Oxford Vaccine Group (OVG), Department of Paediatrics,  University of Oxford, was approached in October 2014 to conduct a ‘first in human’ study of an Adenovirus 26 viral vectored vaccine candidate, given in heterologous prime-boost combinations with a multivalent MVA-vectored vaccine (MVA-BN-Filo). Within 3 months, following an expedited approval process and an extraordinary response from the OVG clinical trial team and the Oxfordshire community, all 87 participants had been recruited. The results from this EU-funded study, recently published in the Journal of the American Medical Association (JAMA), revealed that 97% of recipients of AD26.ZEBOV developed glycoprotein-specific antibodies.

Over half of these participants developed a specific T-cell response and these responses were enhanced by administration of the MVA-BN booster dose. Notably, eight months following the priming vaccination, 100% of Ad26.ZEBOV/MVA-BNFilo recipients maintained Ebola-specific antibodies, while vaccine-induced T cell responses persisted in 77-80%.

This rapid data provision was vital in informing the development programme of this vaccine regimen which is now being evaluated in a Phase II study by the Oxford Vaccine Group, and in eight other Phase II and III clinical trials in North America and Africa.