Development of the ChAdOx vaccine platform
In the early 2000s, under the leadership of Professor Adrian Hill, the Jenner Institute performed several clinical trials of candidate malaria vaccines. These tested a series of different emerging vaccine technologies.
The most promising results were obtained using a disabled version of an adenovirus (a type of common cold virus – in this case, one which affects chimpanzees rather than people) 1. That vaccine candidate had been developed in partnership with an Italian company, Okairos 2,3, building on the pioneering work of Hildegund Ertl, James Wilson and colleagues in Philadelphia. The chimpanzee adenovirus-based malaria vaccine was partially effective, and Okairos was later taken over by the major pharmaceutical company, GSK.
In parallel with the work on malaria with Okairos, the Jenner initiated a project to produce its own chimpanzee adenovirus vaccine platform ‘in house’, giving it the freedom to apply the promising technology to multiple other diseases, independent of any industrial partner. Hill contacted a Swedish scientist, Göran Wadell, who had collected a set of samples of adenoviruses from chimpanzees.
Starting from a sample of a virus known as ‘Y25’ provided by Wadell, a Jenner graduate student (Matthew Dicks, working with senior virologist Matthew Cottingham) created and performed early testing of the ‘ChAdOx1’ vector 4. ChAdOx1 differed from Y25 in that key genes needed for the virus to multiply in human cells were completely deleted, and in that Dicks exchanged one of the Y25 virus’ ‘non-structural’ genes for one from a human adenovirus, which would make the virus easier to manufacture.
Over this time, the Jenner had developed the infrastructure and organisational capability to produce and test multiple adenovirus-vectored vaccines against a range of diseases. Support from the Wellcome Trust allowed the establishment of a ‘Viral Vector Core Facility’ which could make small quantities of many new vaccines for early pre-clinical tests. Hill led re-purposing of the University’s Clinical Biomanufacturing Facility, which had been set up in the 1990s by Geoff Hale and colleagues to manufacture ‘clinical grade’ monoclonal antibodies, to instead make vaccines for first-time-in-human clinical trials.
Putting these capabilities together with the clinical trial expertise built by the malaria programme provided an ‘end-to-end pipeline’ which allowed candidate vaccines to be taken from the drawing board, through laboratory studies, into clinical trials in the UK and Africa.
Multiple Jenner researchers made use of this pipeline to develop and test chimpanzee adenovirus vectors against a range of diseases. Examples included further malaria vaccines (led by Simon Draper5-7), influenza (led by Sarah Gilbert8) and tuberculosis (led by Helen McShane9). Hill & Gilbert founded a spinout company, Vaccitech Ltd, which licensed the right to use the technology for certain diseases.
In 2014, during the West African Ebola outbreak, the Jenner was involved in the first ever clinical trial of an Ebola vaccine, a chimpanzee adenovirus-based vaccine which had been developed by the US National Institutes of Health and Okairos, then acquired by GSK. Using the organisational platform and experience built up by its previous work with similar vaccines, the Jenner team was able to contribute to getting the first trial participants vaccinated very quickly.
Following the Ebola outbreak, international research funders established the Coalition for Epidemic Preparedness Initiatives (CEPI) to develop vaccines against other viruses which might cause future outbreaks. The UK Vaccines Network channelled government funding into similar projects within the UK.
Applying the Jenner’s ChAdOx1 platform to such diseases was a logical step. Arturo Reyes-Sandoval, Sarah Gilbert, Teresa Lambe and George Warimwe each led development of ChAdOx1-based vaccines targeting CEPI priority pathogens 10-14. A team led by Sandy Douglas developed a simple method of manufacturing any vaccine based upon the ChAdOx platform, choosing techniques suitable for scale-up and transfer to larger-scale manufacturing facilities if required in an outbreak 15.
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