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The Oxford/AstraZeneca vaccine has been crucial for fighting covid-19 in the UK and many low-income countries. The unprecedented speed of its manufacture was only possible because the technology underpinning it had been in development for years before the pandemic struck, by a team of scientists at the University of Oxford.

The research was led by Sarah Gilbert, working alongside a team including Teresa Lambe, who helped design the vaccine鈥檚 genetic code, and Catherine Green, who helped manufacture the first batches of vaccine used in trials. The trio spoke to Clare Wilson about the rollercoaster of events behind this historic achievement.

Before the pandemic struck, which diseases were this type of vaccine being developed against?

Teresa Lambe: In 2013, there was an Ebola outbreak. After that, the World Health Organization and a number of bodies put together a hit-list of viruses that they wanted vaccines against. We tried to make vaccines against all of those: Ebola, Zika, Crimean-Congo haemorrhagic fever, Nipah virus, Lassa virus and Middle East Respiratory Syndrome (MERS). On the list of pathogens of concern, there was also 鈥淒isease X鈥� 鈥� the unknown. We always knew we had to have something that we could go quickly with. And that was our ChAdOx1 adenovirus platform [that eventually became the Oxford/AstraZeneca covid-19 vaccine].

When did you realise you might need to make a vaccine against covid-19?

Lambe: I鈥檝e got a brother in China, so I started to follow tweets around a virus that was transmitting in China. I thought it was probably going to be influenza; that鈥檚 where I would have put my money on. Then its identity became known in early January. Because we had the mechanisms in place, we decided to press the accelerator and go.

How fast did you act?

Lambe: The DNA sequence arrived in my inbox quite late Friday night on 10 January [2020]. You have to order the DNA for your antigen. Myself and a colleague spent most of the weekend using the information that we鈥檇 received to design the last piece of the puzzle to make the vaccine. On Monday, we were ready to order it. There was dialogue about whether we should pay for expedited delivery. It was a minuscule amount in the grand scheme of things. In the end, we went for the faster delivery.

Sarah Gilbert: We were interested in how quickly we might be able to make a vaccine against a brand-new pathogen, understanding that it might turn out to be an intellectual exercise. I spent a huge amount of time during those increasingly strange weeks attempting to secure funding. We decided we just had to get on with it, spending money we did not yet have. It would be an understatement to say things escalated fast.

Vaccine sceptics say you went too fast.

Gilbert: We were taking financial risks, we were never taking safety risks. In normal times, we would wait for data to come before we start the next step. The difference was, last year, we started each part of the work at the earliest possible opportunity, knowing that if the work that had gone before didn鈥檛 turn out as we had hoped, we might have to just scrap something and go back and start again.

How did working so hard affect you?

Lambe: We didn鈥檛 hold back. People didn鈥檛 take breaks, we were working long hours 鈥� 12, 14-hour days 鈥� people worked at weekends. I have two children and there were periods over the last year where they would call me Dad because they were so used to saying Dad instead of Mum. But I wanted to make a vaccine and I wanted to make it fast. I didn鈥檛 know if we needed it or not, but if we did, I wanted us to be in the best position we could be in.

Did you feel nervous when the vaccine was given to the first volunteers?

Lambe: It felt surreal. It was in April during the first lockdown and I was still coming into work every day, unlike a lot of other individuals. My walk to work was very, very quiet because there was no traffic on the road. I remember coming home on the day the first person got vaccinated and being slightly overwhelmed.

Catherine Green: For us, the big day was the day before when we certified the batch. The trial had been planned to the minute like a military operation. We were waiting for the final results to come back [to make sure] that it鈥檚 good enough to go into people. We were waiting and waiting and waiting. The test results came back that it had got the all clear. So we had a 鈥淧hew!鈥�.

How did you feel when the positive results were announced that led to approval?

Lambe: When I was told the results by the lead statistician 鈥� she鈥檚 very diligent and she was [slowly] bringing me through the results 鈥� I made her stop and tell me whether we had efficacy or not. Then she went back to bring me through all the different nuances, and it didn鈥檛 go in. I was very, very happy.

Gilbert: I was confident we would get a good immune response to the vaccine because we鈥檇 already done clinical trials with a vaccine against MERS made in the same way given at the same dose. But what nobody knew was how strong that immune response had to be to protect people against coronavirus. Now, with the real-world effectiveness data coming out, there鈥檚 a lot more information about the really high levels of protection from the vaccines against hospitalisation. That鈥檚 what really matters.

Green: I think the real-world efficacy, for me, has been the one that hits home. I think the estimation this week for England was 27,000 deaths prevented by the vaccination programme since the beginning of the year, and that鈥檚 27,000 people鈥檚 grandmas and grandads still with them. That鈥檚 huge. For me, that鈥檚 been the data that was emotional.

How did you feel when the rare blood-clotting side effect emerged?

Lambe: With any medicine or any vaccine, you will get rare side effects. Because they鈥檙e so rare, they鈥檙e not necessarily going to [be revealed] even in trials the size of the one that we鈥檝e done, which was over 20,000 individuals. We need to delineate what is causing the rare side effects and that hasn鈥檛 been fully delineated.

Gilbert: Because it鈥檚 so rare, it makes it difficult to understand what鈥檚 really going on, whether the events were happening above the background rate. At one time, Europe was reporting that it was a phenomenon happening in women and not in men. That turned out to be because they were vaccinating predominantly women. The Joint Committee for Vaccination and Immunisation has been continually monitoring the situation and making its risk-benefit analyses, which change as the situation changes. We still have many countries with high rates of transmission that really need vaccines. They need to do their own risk-benefit analysis.

Was it hard seeing this risk emerge?

Lambe: There have been lots of very hard parts throughout this whole journey. We鈥檝e been living in somewhat of a goldfish bowl for the last year and a half. At times, that has been difficult to deal with. And when there were around the death of our first vaccine trial volunteer [who was in fact alive and well].

Green: I was really disgusted by that, because that鈥檚 somebody鈥檚 family. I don鈥檛 know what the motivation is behind the person that would make that claim and circulate it.

What can we learn from the past year?

Gilbert: For outbreaks and pandemics, we need to have access to flexible funding so if something like this happens again, we鈥檙e able to go through all the process without having to spend a lot of time trying to raise the money to do it. And we haven鈥檛 had infrastructure investment. Catherine runs an excellent, very small, frankly rather old-fashioned manufacturing facility. It does a great job, but it can鈥檛 produce very much vaccine. If we鈥檇 had an expanded and modernised clinical biomanufacturing facility, our lives would have been so much easier in 2020.

What are you doing now?

Gilbert: We鈥檝e been working closely with AstraZeneca to optimise the pipeline for making new vaccines against variant viruses. We started months ago, getting all that set up again, not knowing if we鈥檙e going to need to switch. But again, we have to do the work so that if we do need to switch, we can. If we don鈥檛 do the work, we don鈥檛 have the opportunity. The clinical trial of the beta variant vaccine has started, in Oxford and other parts of the world. And we鈥檙e trying to go back to work we were doing before the pandemic on vaccines against other diseases.

Green: Those other diseases haven鈥檛 gone away.

Have you had the Oxford/Astra Zeneca vaccine yourself?

Gilbert: Yes.

Green: I had it at a football stadium. That was a marvel of organisation and volunteers and of people feeling that this might be the beginning of the light at the end of the tunnel. I did say: 鈥淚鈥檓 so proud because I made that.鈥�

Lambe: I haven鈥檛 told anyone which vaccine I鈥檝e had. I recommend anyone to take whatever vaccine they are offered, in line with whatever their government is suggesting. My parents have had two different vaccines 鈥� but the fact that they鈥檝e been able to have any vaccine is huge.

I鈥檝e had your vaccine. Thank you.

Gilbert: You鈥檙e welcome.

听

This article is based on an interview with Lambe and a separate interview with Gilbert and Green.

Gilbert and Green鈥檚 book Vaxxers: The inside story of the Oxford AstraZeneca vaccine and the race against the virus will be published on 8 July by Hodder & Stoughton.