‘The longest week ever’: the story behind the latest COVID-19 vaccine success
by Guest Author on 26 Nov 2020
The new vaccine, ChAdOx-1 nCoV19, developed by the University of Oxford and AstraZeneca has generated international headlines this week. This breakthrough was the result of both long and short-term funding support, from UK Research and Innovation councils with the Medical Research Council at the heart. Sarah Gilbert, Professor of Vaccinology at the Jenner Institute and lead scientist on the vaccine project, describes what the journey has been like so far.
The story behind this week’s successful trial results started back in January when we first heard reports of a new respiratory disease emerging in China.
At the time we didn’t know whether the outbreak would just fizzle out, or if it could be something big and important. Our experience developing vaccines for other outbreaks taught us that if there’s a chance it’s going to be big then we had to start working on it straight away, even knowing that it might not be necessary.
It soon became clear that the pathogen responsible for COVID-19 was a novel coronavirus, SARS-CoV-2, and that there was a high risk that the localised outbreak would turn into a global pandemic. As the death toll rose and countries began to lockdown, we were already at work developing a vaccine against the new virus.
From MERS to COVID-19
Our previous work developing an adenovirus-based vaccine against the Middle Eastern Respiratory Syndrome (MERS) coronavirus, funded by the UK Vaccines Network, a partnership between the Department of Health and Social Care and UKRI’s Medical Research Council and Biotechnology and Bioscience Research Council, provided an obvious platform from which to start.
The task of designing a vaccine was made easier by the fact that there’s only one protein on the surface of the virus – the spike – meaning that we didn’t have to spend a lot of time thinking about which antigen we were going to use.
We also had the chimpanzee adenovirus vector from the MERS vaccine, which we’d tested in clinical trials so we knew it was safe and could provoke immune responses. So once we had the sequence of SARS-CoV-2, following its release by Chinese investigators, it was a case of ‘copying and pasting’ the genetic code for the spike protein into our harmless chimp adenovirus to create the ChAdOx1 nCoV19 vaccine.
Long-term funding through UKRI, adding up to more than a decade of investment, has been key to developing the viral vector vaccine platform and optimising our manufacturing methods. This meant that all the pieces were in place for us to be able to develop a novel coronavirus vaccine at speed.
The COVID-19 vaccine work was additionally supported by £2.6 million UKRI/National Institute for Health Research (NIHR) Rapid Response grants in March which provided funding to conduct pre-clinical investigations and a phase I/II trial and scale up the vaccine to 1 million doses by summer 2020. The trimmed-down application process, with no unnecessary bureaucracy and a very fast turnaround, was very helpful at such a pressured time.
Moving at speed
People often think of vaccine development as being all about immunology, but we need to think about the manufacturing side as well. It was very important that not only could we create a safe an effective vaccine, but also that we could make it in very large quantities for a low price, and that it could be stored in the fridge to be used in a wide range of global health situations.
We’ve spent a lot of time planning how to move as quickly as possible from the moment a new pathogen is identified through to clinical trials, such as speeding up the lengthy quality control processes required during vaccine manufacture without compromising safety.
I co-direct the multidisciplinary Future Vaccine Manufacturing Research Hub (Vax-Hub), supported by UKRI’s Engineering and Physical Sciences Research Council (EPSRC) and it turned out to be critical for getting the project off the ground quickly – highlighting the importance of funding large-scale, collaborative vaccine manufacturing research. AstraZeneca have also hugely contributed, shouldering much of the large-scale manufacturing burden.
This isn’t something that any one lab, institution or sector can do alone. If we want to make an impact in bringing forward novel vaccines, we should be funding large-scale facilities and consortia of researchers who all have their own role to play but work in a very collaborative manner.
One shot to get it right
Since starting work on the vaccine in January, our team has worked around the clock at an incredible pace.
We haven’t had the luxury of time to make a number of different versions of the vaccine and pick the best. There is only one clean room in our manufacturing facility, meaning we only had capacity to make a single candidate. We just had to hope that the one we picked would work.
By early February we’d tested a lab version of the vaccine in mice and quickly saw very strong immune responses, so we had a good idea that the approach we had taken was going to work. But while we had our expectations, we still had to confirm them.
Every experiment we did was like ticking another thing off the list: is it genetically stable? Yes. Can it be manufactured with a good yield? Yes. Is the safety profile what we would expect? Yes. When the results started coming through from the clinical trials, there wasn’t a big ‘Eureka!’ moment, but yet another confirmation that things were working as we hoped they would.
Although the scientific part of the vaccine development process has gone smoothly, we’ve had a lot of practical problems to solve along the way. Implementing social distancing and other measures to protect our team and trial participants has been a major challenge, as well as working across multiple countries and with multiple partners.
We’ve had to use a lot of videos instead of face-to-face presentations for giving information to the volunteers, and also work out how they could safely wait after receiving the vaccine to check for any adverse effects.
Sadly, this also meant I wasn’t able to witness the first volunteer in the clinical trial receive their initial dose in April as we were in lockdown at that point.
Carrying out a project on this scale has taken hundreds of researchers, technicians clinical and non-clinical staff across multiple sites, along with tens of thousands of volunteers.
I’m incredibly proud of the way the whole team has worked together. We’ve got a lot of really highly motivated people both in the clinical centre and the lab, including many who don’t normally work in this area. We’ve also been able to take over lab space from our colleagues here in Oxford in order to maintain social distancing, which has been much appreciated.
Everyone has pulled out all the stops, working very long hours over evenings and weekends and doing the kind of jobs that often don’t get noticed, like organising and phoning all the trial volunteers and managing the complex, ever-changing budgets.
And, of course, we must thank all the volunteers who have taken part in the trials in the UK, Brazil and South Africa. A lot of participants told us that they got involved because they wanted to do something positive during this difficult time, and we’re really grateful that they did.
Good news, but the work goes on
The positive results from the phase 3 trials of ChAdOx1 nCoV19, together with recent good news from trials of RNA-based vaccines from Pfizer/BioNTech and Moderna suggest that vaccination against this new coronavirus is possible.
Our analysis of the trial data so far shows that the vaccine is 70% effective, meaning that it reduces the incidence of disease in people receiving the vaccination by 70%. By way of comparison, flu vaccines are around 40 to 60% effective, so this is a significant positive result.
However, this figure is an average across two different dosing schedules. While two high doses of our vaccine are around 62% effective, an alternative dosing schedule of one low and one high dose seems to be around 90% effective. We’re currently following up with the collection and analysis of more data from the trials to establish the level of protection and optimise the dosing schedule.
Although we still have much more work to do, we have taken a moment to celebrate the latest results. At about five o’clock on the day the latest results were announced we had a socially distanced glass of champagne in the institute with others joining us on Zoom. I had that Friday feeling when you think, ‘Oh, I can wind down now and enjoy the weekend’ and then it dawned on me it was only Monday! It really has felt like the longest week ever.