Consortium Members Work To Deliver UK's First COVID-19 Vaccine As Quickly and Safely As Possible
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A consortium led by the Jenner Institute at Oxford University is working to rapidly develop, scale-up and manufacture the potential COVID-19 vaccine, ChAdOx1 nCov-19, or ChAdOx1, for fast-tracked clinical trials.
ChAdOx1 is anticipated to be the UK's first COVID-19 vaccine and is one of the "frontrunner" vaccines currently in development across the globe. The consortium aims to deliver the vaccine as quickly and as safely as possible, hoping to develop and manufacture the candidate in multiple batches to support a 1million dose scale batch size by summer 2020.
Cobra Biologics (Cobra), an international contract development and manufacturing organization for biologics and pharmaceuticals, recently joined the consortium.
Technology Networks spoke with Tony Hitchcock, Technical Director at Cobra Biologics to find out more about the consortium's aims, how the vaccine works and to gain insights on realistic timelines for vaccine development and manufacturing.
Molly Campbell (MC): Can you tell us about the consortium's development, and it's aims?
Tony Hitchcock (TH): The aim of the manufacturing scale-up consortium is to enable the fastest and safest route to provision of the ChAdOx1 nCoV-19 vaccine candidate. Under normal circumstances, work on manufacturing scale-up would only take place after clinical trials show both safety and efficacy. Other teams at the University of Oxford are leading on pre-clinical development, manufacture for clinical trials and the clinical trials themselves. This consortium is working in conjunction with those other functions to give us the best chance of delivering a vaccine as quickly and safely as possible. This should minimize the delay between positive clinical trial results and vaccine deployment.
The manufacturing scale-up consortium is being led by Dr Sandy Douglas and his team from the Jenner Institute at the University of Oxford, who work closely with other teams at the University. Dr Douglas’ group have experience with the ChAdOx vaccine platform and have spent several years working on a GMP-compatible, scalable manufacturing process. Once the scale of the COVID-19 threat became apparent, several commercial and NGO partners, including Cobra Biologics, joined the consortium to speed up process development and technology transfer to GMP manufacturing facilities.
MC: What expertise will Cobra Biologics bring to the consortium?
TH: Cobra has over 25 years’ experience of developing manufacturing processes for viral vectors, 21 of these as a contract manufacturer. Our experience covers all areas, from the development of manufacturing processes, transfer and scale up of processes into GMP manufacturing and the production of viral vectors for clinical use, in addition to the analytical and quality systems required to support these development and manufacturing activities. Additionally, our facility in the UK has been designed specifically to handle these types of products. We are one of the few facilities in the UK approved to manufacture viral vectors for clinical use at the required production scales.
MC: Can you tell us about the adenoviral vaccine candidate ChAdOx1? How does it work against SARS-CoV-2? What preclinical results have been generated thus far?
TH: Coronaviruses like SARS-CoV-2 have club-shaped spikes on their outer coats. Immune responses from other coronavirus studies suggest that these are a good target for a vaccine. The Oxford vaccine contains the genetic sequence of this surface spike protein inside the ChAdOx1 construct. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.
Chimpanzee adenoviral vectors are a very well-studied vaccine type, having been used safely in thousands of subjects, from one week to 90 years of age, in vaccines targeting over 10 different diseases. The ChAdOx1 nCoV-19 vaccine has performed similarly to other ChAdOx1 vaccines in preclinical studies.
MC: Under normal circumstances, vaccine development can be a lengthy process. How has Cobra Biologics worked to facilitate the development and testing of ChAdOx1?
TH: We are working very closely with the team at Oxford and all the partners in the consortium alongside the MHRA to build on the production process that has already been developed by Dr Douglas’ group to establish a robust process at the planned production scale. The aim is to parallel track as many activities as possible, including equipment procurement, and to share and pool the knowledge and experience of the consortium to limit both the required development activities and to identify and mitigate the potential risks that can be encountered in the development and manufacturing scale up.
MC: The consortium expects to "develop and manufacture ChAdOx1 in multiple batches, to support a 1million dose scale batch size, by summer 2020". Can you discuss the challenges associated with large-scale vaccine manufacturing?
TH: The challenge to make 1 million doses of any vaccine is dependent, to a large degree, on the dose size required and the productivity of the production system. A key point about the adenoviral vaccine developed by the Jenner institute is that it has been shown to be both potent and productive and is very well suited to the production of large quantities of vaccine. The dose sizes for this type of vaccine for other coronavirus-based infections such as MERS and SARS are in the region of 5x1010 viral particles. It is possible to make such quantities of viral particles in 0.2ml of culture, or 5 doses /ml of cell culture. Therefore, it should be possible to make 1,000,000 from 200L of cell culture, which is not uncommon. The ambition is a realistic one and should be achievable, and the consortium is looking at establishing production of these scales at multiple sites.
In terms of the specific process, the challenge will be to ensure the robustness of all stages of the process from the cell culture through to the final formulation of the product. A key point about viral vectors is that they are very large and complex, making them difficult to characterize and analyze from a manufacturing perspective. We are therefore dependent upon controlling the manufacturing processes to ensure that product quality, safety and functionality are achieved.
The key challenge will be to develop sufficient knowledge of the manufacturing process to enable further scale up and process transfers to manufacturing sites whilst retaining the essential quality attributes of the vaccine. If we achieve this, then the production of 1,000,000 doses is achievable
MC: The ChAdOx1 consortium is currently recruiting individuals in the UK to trial the vaccine’s efficacy. Are you able to expand on the primary/ secondary outcomes of the trial at this time?
TH: The primary outcome of the Phase I/II clinical trial for which we are currently recruiting is to assess the safety of the vaccine in healthy individuals. However, results from these volunteers will also be used to assess efficacy, alongside data from the Phase III clinical trial which is due to enroll 5000 participants. Efficacy here will be assessed by cases of COVID-19 in the vaccinated and unvaccinated groups.
MC: What are the biggest challenges in developing a vaccine against COVID-19?
TH: Our ability to determine vaccine efficacy will be affected by the amount of virus transmission in the local population over the summer. If virus transmission has stopped, then it is impossible to assess whether the vaccine can prevent infection. Currently it is not possible to identify who has already been infected, and if the virus is spreading quickly throughout the population it might be difficult to find unexposed people to take part in the trial.
Conducting trials after the peak subsides presents another problem, because so many people will have developed a natural immunity by then, and the amount of transmission will have dropped so that those who are still not immune will take longer to be exposed to the virus.
Tony Hitchcock, Technical Director at Cobra Biologics, speaking to Molly Campbell, Science Writer, Technology Networks.