Hospitals in Wuhan, China reported treating dozens of patients with pneumonia from an unknown source, December 2019. The new coronavirus was quickly identified as the cause of the disease.
Teresa Lambe, associate Professor, Jenner Institute My brother was born in China so I followed any break or emerging pathogens. This was likely another strain of influenza, which I recall thinking about very early.
Sarah Gilbert, Sad Professor of Vaccinology, Jenner Institute [Before Covid], I was working on vaccines for a variety of emerging pathogens, including Mers, Nipah, and Lassa. We had also applied for funding to study preparedness for the unknown pathogen, disease X. We were not granted funding, so none of these plans were put into place.
Andrew Pollard, Director, Oxford Vaccine Group We all knew that this was going to become a pandemic.
Media reported on 11 January 2020 the first death caused by what would become known as SarsCoV-2 or Covid-19. Zhang Yongzhen, a Chinese virologist, published the virus' genome sequence online that day. Lambe received the genome via email early Saturday morning.
Lambe We knew that it was coming and had already discussed what to do. Over the weekend, we created [the vaccine].
Sarah Gilbert: Were no big corporation. Photograph by Manuel Vzquez/The Guardian
Gilbert Before the genome was created, we knew that it was a new Coronavirus. Not the original Sars. Mers. Because it was a coronavirus we knew that the gene we needed contained the spike protein. This is what you need to generate an antibody response.
Cath Green, the head of the clinical biomanufacturing laboratory Sarah [Gilbert], had made a vaccine for Mers and knew exactly what her vaccine against the coronavirus would look like. They adapt the DNA sequence from the Chinese laboratory's coronavirus spike protein to fit into our system. Jenner lab takes that sequence and inserts it into a larger sequence which includes the adenovirus gene. They sent me a small tube containing a few micrograms DNA. That was my job.
Gilbert At that stage, it was a demonstration project.
The World Health Organization declared the new coronavirus epidemic a global health emergency on 30 January 2020. The virus had already spread to many countries, including Japan and Taiwan, by that time, and the US closed its borders to Chinese tourists. On the same day, the UK confirmed the first case.
Pollard Despite the fact that vaccines can take up to 15 years to make, we knew it was a serious problem. We needed to figure out how to make that happen before the pandemic kills millions.
Mid-February saw Gilbert's group at the Jenner and Pollards Oxford Vaccine Group join forces to concentrate their efforts on developing their vaccine candidate. Cases were rapidly spreading worldwide by then.
Pollard We all realized that we had to work together to accomplish something quickly and on a large scale.
Federica Cappuccini is a senior postdoctoral researcher. There were many emails asking, "What's your availability?" What skills do your have? What can you do to help?
Hannah Robinson, clinical delivery leader I can recall that when we first met, one of the scientists said that every day, if there wasn't a vaccine, that would mean that 10,000 people were dying.
Green and her collaborators inserted DNA containing instructions for making the spike protein in a culture of genetically modified human renal cells.
Green The DNA must be taken and inserted into human cells under controlled conditions. The next step is to identify a "clone", a cell that has begun to produce the vaccine. This can be done using one copy of the DNA that we have inserted. Because the vaccine is a virus, it multiplies in the cell. Eventually, the cell explodes and the virus is released. It can then infect surrounding cells. One virus can fill up a cell. It then pops and infects 100 more cells. Then they explode and infect 1,000 more cells. Even though we started with just one virus particle, we ended up with 300ml solution containing vaccine. Each dose of AstraZeneca vaccine found in someone's arm today was derived from our first clone. It was D8.
It was administered simultaneously to animals to test its safety and ability to induce an immune reaction. The vaccine was given to mice and rats at the Pirbright Institute, Surrey, and to rhesus macaques at Rocky Mountain Labs, Montana, USA. The Oxford scientists began to plan a phase 1 clinical trial.
Pollard You might get great results and then find funding to finance the manufacturing. This could take up to 18 months. Then you can start the phase one trial. It is important to cross-pollinate all of these processes. The animal studies began in February and the manufacturing started for human trials by March. We didn't have any data from animal studies.
Andrew Pollard: It is important to be prepared for new versions. Photograph by Manuel Vzquez/The Guardian
Robinson You will need to submit to the MHRA [Medicines and Healthcare products Regulatory Agency] and to the ethics committees. All the documentation required to conduct a trial. These documents must be reviewed and written, then submitted. This would take about six months in a pre-pandemic situation.
Pollard This was a priority for the MHRA, so more people were added to it. All the information was submitted; seven days later, they could give approval.
Boris Johnson declared that the UK would enter its first lockdown on 23 March 2020 after cases reached 6,650 per day in the UK. All non-essential businesses were shut down and all non-essential employees were asked to stay home to stop the spread of the virus. On the same day, the government gave a grant of 2.2 million to Oxford for their research.
Maheshi Ramasamy is a senior clinical researcher. I am a consultant in infectious diseases. My day job involves looking after patients in the hospital. We saw our first cases in Oxford just after the February half-term. As a precaution, we started to see one or two cases. In mid-March, I arrived on the ward. We had only one Covid on Friday; now we have 11. They were older and more frail than they used to be, and were rapidly dying.
Lambe I can remember walking from my house so peacefully, not needing to look before crossing the street because there weren't any cars. It was quite eerie.
Green Everything came to a halt. We had difficulty finding disinfectant and masks. We have a lab and hand sanitizer is basically ethanol, hydrogen peroxide, and some glycerol. So we made a few litres of it and splashed it around.
Researchers at the Jenner Institute. Photograph by Manuel Vzquez/The Guardian
Pollard The NHS did not have any PPE. Thermometers were needed for volunteers. There was none in Europe.
Gilbert I can recall a conversation I had with Matt Hancock. He asked me, "What do you need?" I replied, PPE.
Ramasamy It was really hard to work in a hospital. This was a new, terrifying disease that we had never experienced before. It was a new disease that we didn't know how to deal with. One moment was when someone said to me, "Is this how the end of the universe feels like?"
The first phase of the vaccine was almost ready for clinical trials.
Green This stage requires that you centrifuge the material using a gradient. All of the vaccine lines up in a single layer. It's obvious. Kathy, a member of my production team, came out to say: Look at these babies! It was that day that we realized we had enough and could get it in somebody's arm in just three weeks. It was amazing. That was great.
Pollard The vaccine was already approved ethically by that time. We gave the first dose the day after we received the successful animal trials results.
Elisa Granato was given the first dose of the Oxford vaccine (then known as ChAdOx1) on 23 April. Granato is a microbiologist. Fake news websites spread the rumour within 48 hours that Granato had died due to side effects of the vaccine.
Pollard She didn't, of course.
Gilbert Gilbert's family had to be informed because they were hearing about her death from friends and family.
Pollard Elisa was interviewed by Pollard on Sunday morning by the BBC. They were able to prove that she was still alive. The UK media saved the day in this case. However, there are still fake news stories that have eroded vaccine confidence.
Lambe I don't think I understood how important it was to communicate with the public until almost halfway through.
Teresa Lambe: This was the first time I thought it was another strain of influenza. Photograph by Manuel Vzquez/The Guardian
Gilbert I'm trying to let people know that Gilbert is not another type of being. We weren't a large corporation and we didn't have to work with big pharma. We work with big Pharma because they have a valuable job to do.
Lambe They are not evil. They are really nice people.
Oxford University and AstraZeneca, a British-Swedish pharmaceutical firm, signed a contract to mass-produce vaccine on 30 April. The company also agreed to Oxford's demand that the vaccine be provided at no cost to developing countries during the pandemic.
Gilbert We were not involved in these discussions. Other people at the university were involved. It was a time when we were completely out of our minds about what we were doing.
Lambe It was an absolute for everyone in the team.
Pollard We wanted a vaccine that could reach all corners of the globe. To do this, a large pharmaceutical company is required. AstraZeneca was the right choice. Their willingness to do this not-for profit is the most remarkable thing about them. It is almost impossible to imagine a business thinking that this was an acceptable thing.
Phase 1 trials had shown a positive antibody response with no side effects. Plans were made to start a phase 2 or phase 3 trial simultaneously in the UK, South Africa, Brazil, and the USA. AstraZeneca was also purchased by the United States, UK, and other countries. Clinical trials had been initiated by rival companies Moderna and Pfizer.
Pollard The first lockdown had the greatest impact on the suppression of the virus. It was obvious that there wouldn't be enough cases when the trials started. There were two pieces of advice for phase 2 and 3, which were being planned through April. The first was that we don't know what the next wave might look like so we should be geographically dispersed. It could be in the UK. Or it could be that we need to be in South Africa and Brazil. Another reason was to ensure that we didn't hear from people in Africa, South Asia, or Latin America saying, "Well, this vaccine was only tested in Europe."
The vaccine supply was very limited during the trial. This led to some extraordinary measures.
Robinson I can recall being on the phone with Andy [Pollard] Sunday afternoon with the Italian manufacturers. We decided to charter a plane to get the vaccine to the UK so that our UK team could label the vaccine, so we could run the clinic the next day.
It was discovered that the Italian vaccine doses were different from those produced by Greens Lab in Oxford due to technical complications.
Gilbert There are many ways to measure the vaccine's concentration. Advent, the Italian manufacturer, uses one test [assay] while we use another. We discovered that the results of the two assays were giving us different results when we received the batch from Italy. One gave us a result twice the other. We had to choose which concentration we would use for the clinical trials. We could have given half the dose if we choose one. If we chose the other, we could have given twice as much. We chose the safer option and gave the dose where, if we were to be wrong, it would only be half the dose.
Pollard We returned to the MHRA, and they agreed that we should adjust the dosage. We continued the trial. The regulator's flexibility in allowing us to adjust was a huge saving that saved many lives.
As the world waited for news on a possible vaccine this summer, the Jenner Institute was the focus of unrivalled attention.
Charles Parkins is the Old Road Campus facilities manager. There were demonstrations outside with a man and his supporters making lots of noise and accusations. There were a few of them; university security and the police dealt with them. The person who shut down the loudmouth was actually one of the workers on the site. He lost his voice after that.
Oto Velicka was senior buildings and facilities manager. We received numerous threats emails, tweets, and phone calls. This forced us to call the police.
Charles Parkins: There were people protesting outside. Photograph by Manuel Vzquez/The Guardian
Parkins 1 thief gained entry to the building. He searched through the offices and found two new computers. Then he left. Strangely, a second or third day later, another man knocked on the front door, saying, I want you to come in. I called security thinking it might be a bomb or something. They said Charles, it was four new computers.
The world celebrated Pfizer/BioNTech's announcement of their vaccine being 90% effective on 9 November 2020. Moderna declared its vaccine's 94.5% effectiveness on 16 November. A few days later Oxford had enough data to release its initial results on the Oxford/AstraZeneca vaccination's efficacy. The vaccine was 70% effective in preventing Covid-19. The data revealed that the vaccine was 70% effective in preventing Covid-19. However, only 62% of those who received two full doses were effective. A smaller group receiving a half-dose followed by a full dosage saw an increase of 90%.
Cappuccini
Pollard As I sat here, the members of the data safety oversight board went through the data together with me. We had worked so hard to make everything ready, and I was tired. It was an incredible moment, as no one from the team was there. I was the only one who saw the data for the very first time. Sarah Gilbert was my contact and I told her the results.
Gilbert On Saturday night Andy Pollard called me. He had told me to not expect results until Sunday. I said, "Why can't you just tell us the result?" I had expected a number of x%, but it was much more complex than that. It was efficient, and that was fantastic.
Pollard Pollard Because of exhaustion, the emotion was probably less than it should have been.
Mustapha Bittaye - Every effort, every night of sleepless nights have paid off. Photograph by Manuel Vzquez/The Guardian
Mustapha Bittaye was a postdoctoral researcher. I knew that the vaccine would be used around the world. This vaccine will be a blessing for my family in Gambia. When I learned about the effectiveness results, it made me so happy. It gave me the feeling that all my efforts, no matter how long they were, had paid off.
Cappuccini These vaccines will also be in the hands of those we love,
AstraZeneca published its findings on 23 November. The results were complex and led to criticism from the scientific community. They were not made immediately available by AstraZeneca, which communicated them via press release.
Gilbert AstraZeneca is subject to a legal requirement: any data that could affect their stock prices must be disclosed immediately before the markets open. We prefer not to release data via press release. We want peer-reviewed publications. That had to be done.
Ramasamy Ramasamy, the low dose thing was a bit misleading. We looked back at the data and found that it was the time between doses that was most important. The longer the interval between the first dose and the second dose, which is typically four to twelve weeks, the better your immune response.
The vaccine was approved by the MHRA for UK rollout on 30 December 2020. Hundreds of thousands of doses were given to the UK's at-risk populations in January during the second wave. Due to manufacturing issues, supplies to the EU were delayed which triggered a political crisis. To make matters worse, the French president Emmanuel Macron claimed that the vaccine was ineffective for people over 65. This claim is based on a dearth of data from older age groups.
Pollard There were two main reasons we did not have enough cases among the older age group. The first was that older adults in all countries were more cautious in dealing with the pandemic. This meant they were less likely to be exposed. There was no information about vaccines. Our data safety monitoring board stated that they were more concerned about older adults and recommended sequential vaccination. You should look at the safety data and obtain the immune response data before starting your efficacy arm for older adults.
Research building at the Old Road Campus. Photograph by Manuel Vzquez/The Guardian
Gilbert We are not involved in politics because AstraZeneca is. While we were watching the news as everyone else, there is nothing we can do. AstraZeneca had made great efforts to establish manufacturing. These aren't small-molecule drugs. They are difficult to make. This is the first time this has been done at such a large scale, and at such a rapid pace, so it's impossible to predict how long it will take.
Pollard I don't think [supply] could be any better than it currently is, considering how difficult it is to make vaccines.
Lambe More than 90% of all Covax doses contain AstraZeneca. This to me is huge.
Gilbert Since the beginning, our goal has been to create a vaccine that is universally accessible. We have not made any financial profits. We need to ensure that there is enough licensed Covid vaccines available for everyone around the world.
AstraZeneca vaccine was linked to rare blood clots and low platelet count in a small number of patients. Similar cases have also been reported for the Johnson & Johnson vaccine which uses an adenovirus vector. According to current estimates, blood clots could affect one in 100,000 people. Many countries have decided to not offer the vaccine to those of lower income. Low uptake is also due to fear of blood clots in poorer countries.
Ramasamy Side-effects are a part of all drugs. It was something we were monitoring in the clinical trials. We also monitored every participant who had any type of serious medical condition. It is always very distressing to hear about serious side effects as a clinician.
Maheshi Ramasamy - It was the time between doses that was crucial. Photograph by Manuel Vzquez/The Guardian
Gilbert This was difficult because different vaccines were used in different age groups and countries. Europe once said that this was a female phenomenon and not affecting men. It was simply that the vaccine was being given primarily to young healthcare workers, most of whom are women. It is still not understood. There have been many hypotheses and people are still trying to understand them. Because it is so rare, it may take a while to understand.
Pollard In the past year, approximately 1,800 people have died from Covid. When we take into account the side effects of Covid, the death rate for those who were vaccinated is about one per million. It is clear that vaccinations are a good idea from a risk-benefit perspective.
Parvinder Aley is the director of operations. If you were to take any other regulated drug, and believe that the regulators are following their instructions, then this one would be no different. It has been through all of them. We've been through many of these processes. So I can assure you that the regulators have carefully examined this, not only in the UK, but worldwide, and are willing to grant authorisation.
AstraZeneca and Oxford have just begun to test a new vaccine. It is targeted at new variants better, which could be used as a booster shot.
Pollard In mid-December, the first design work started. We are currently in a position to see good protection from the current vaccine against severe diseases that may have arisen from variants. The question that I will ask is: Do you need a new vaccine variant? We need more evidence to confirm my suspicions. Are we required to be prepared? Yes. That is why we are developing new vaccines. We expect to have data by the autumn.
Gilbert It was already known from clinical data that Gilbert was receiving good protection against severe diseases and hospitalization against variants. It's not as if the vaccine suddenly stops working. Public Health England data shows that two doses of the vaccine are as effective as 92% in preventing hospitalization.
Seven Oxford scientists including Green, Lambe and Pollard were honored by the Queen's birthday list in June for their contributions to public health during the Pandemic. The last year has been intense for the Oxford Vaccine Group and Jenner.
Gilbert It has been exhausting. It has been a difficult 18 months. We have had to work together to make the most of it. We have had very little time for other things. In addition to developing the vaccine, we have made every effort to communicate what we know and don't know. This has ensured that any statements we make are supported by scientific evidence. It was frustrating to see that others did not communicate their findings accurately or clearly after all the care taken.
Pollard It was so intense for such an extended period of time. There were no weekends off.
Ramasamy Many people still feel traumatized by their time with Covid patients. It was horrendous.
Bittaye This vaccine was developed in one year. It is the modern equivalent of landing an astronaut on the moon. It is a huge achievement. It all took place thanks to unprecedented collaboration between the public and private sectors.
Lambe We, and many others, have made so many sacrifices during this pandemic. This is not something I want to see the next generation have to go through. It is not something I want to see my children do. It's only a matter time before the next pandemic, because it will happen. It is important to establish processes so that we are better prepared for the next one. I fear that we will try to forget everything we have learned and the sacrifices we made.
