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Panorama 2020 E49
Transcript
00:00Vials of liquid hope coming off the production line, a vaccine developed in
00:06the UK against COVID-19. It could be approved by Christmas.
00:13There's never been a year of progress scientifically like this in my lifetime.
00:19You know it was worth it because we'd worked really hard. I think we all had a little cry.
00:25This is the story of the scientists who designed it, the doctor who led the
00:30trials, the team who helped them, and the volunteers who made it all possible.
00:40I'm the BBC's medical editor and over the past year I've followed their story.
00:46The race to make a vaccine to end the pandemic.
00:55This is the story of the scientists who designed it, the doctor who led the trials, the team who helped them, and the volunteers who made it all possible.
01:05Scientists in China are trying to determine if a new virus strain is responsible for pneumonia.
01:09Authorities have reported 27 cases in total, seven of which are critical.
01:15I have a brother, he was in China at the time, so any outbreaks that happen in China I do tend to
01:21listen and pay attention. The number of cases has increased to 44 with 11 of them in serious condition.
01:28I first read about an outbreak of SARS-like pneumonia from a website that reports on
01:34disease outbreaks. It really caught my attention because we've been thinking about how are we going
01:38to respond when a new virus emerges and it might spread quickly and we don't have a vaccine.
01:44At the beginning of the year the first cases of a mysterious new disease were reported in Wuhan.
01:51Over 5,000 miles away in Oxford this team of scientists thought they might be able to create
01:57a vaccine for it. At that stage it wasn't apparent what type of outbreak this would be
02:04but it certainly had pandemic potential. The information that we needed to design the vaccine
02:11arrived in my inbox the early Saturday morning. The ping woke me up, I still remember.
02:17It was the genetic coding sequence for the virus and what we had that information, that tiny bit
02:23of the sequence from the coronavirus and use that to put into our platform vaccine technology
02:29and then I worked on it over the weekend. So were you working remotely or were you in the lab?
02:35I'm afraid it wasn't quite as glamorous as that. It was pyjama wearing in my bedroom over a computer
02:41trying to get this done with my colleagues and my family didn't see me very much that weekend
02:46but I think that set the tone for the rest of the year. By Monday morning on the 13th of January
02:53the vaccine was designed. Some ominous developments out of China on a new illness. Officials there
02:59have just confirmed the first human-to-human transmission of coronavirus is that it makes
03:06it more difficult to contain the spread when human-to-human transmission is a factor here.
03:13By the middle of January it was clear that that all of the features that you would
03:18really worry about about an emerging infections, you know, no immunity in mankind, no vaccine,
03:24no drug, no diagnostic, an animal virus in a big city just before Chinese New Year
03:31in the winter months and then it was spread by respiratory route by coughing and sneezing over
03:37people. I mean those are all of the features all together that make you worry. As cases rose in
03:45China the new virus caught the attention of Professor Andrew Pollard who runs clinical
03:51trials at the Oxford Vaccine Group. I went to a meeting in France to talk about our work on typhoid
03:59and in the taxi from the airport I went with one of the modelers who's been working with SAGE
04:06and chatted with him about this virus that was emerging from China and he said from the data
04:13they had there was going to be a pandemic that affected the world that was not going to be very
04:18different from the way the 1918 flu was. And in that taxi journey I went from someone who was
04:24aware of a small outbreak in China which was of academic interest to realising that it was going
04:30to change our lives this year and it was a chilling moment. I wanted to get the money to make a vaccine
04:36ready for a clinical trial and then do that first clinical trial and Andy Pollard was the obvious
04:41collaborator to ask from the very early stage to come and help me with that. I head the clinical
04:46biomanufacturing facility which is a small manufacturing suite inside the University of
04:52Oxford. I was thinking about the vaccine manufacturing so that we could go into clinical
04:57trials the clinical testing in animals that we were going to need to do because we needed all
05:01of that and it all had to happen as soon as we could. Sarah Gilbert emailed me to say we've
05:08noticed that there's clearly something big happening in Wuhan and we need to work on
05:13developing quickly a vaccine against that just to give me a heads up that there might be some
05:18involvement required from me. I think probably the first big team meeting we had was a key moment
05:24where a lot of people started to realise that this was going to be something big that we were going
05:29to be working on together. The team could move so quickly because of the template they used to
05:37design experimental vaccines for diseases like malaria, flu and crucially a different coronavirus
05:45called MERS. Each vaccine they create uses a harmless virus which can deliver genetic
05:55instructions to human cells to build an immune response. This template meant that once they had
06:01the new coronavirus code it took just 48 hours to design the vaccine.
06:19A full month after the vaccine was designed the disease caused by the new coronavirus
06:24finally got a name. And it is COVID-19 and I will spell it C-O-V-I-D hyphen one nine.
06:38But getting funding to take the Oxford vaccine into clinical trials was a struggle. That was
06:43really all I thought about for about three months. It was my job to get the money and that's why I
06:48was getting up at four o'clock in the morning to write the next bit of the grant application
06:51and talking to government, talking to other funders.
07:00We expect to see the number of cases, the number of deaths and the number of affected countries
07:08climb even higher. Animal studies would have to be conducted and the vaccine prepared for
07:16human trials. Meanwhile the World Health Organization finally acknowledged the virus
07:22was spreading out of control. We have therefore made the assessment
07:28that COVID-19 can be characterized as a pandemic.
07:38All schools across Britain will close by the end of the week until further notice as the death
07:43toll from coronavirus reached 104. On the 23rd of March the UK was put into lockdown. Without a
07:51huge national effort to halt the growth of this virus there will come a moment when no health
07:57service in the world could possibly cope. That day the government announced funding to support
08:04clinical trials and manufacturing. But lockdown meant significant challenges. Because you couldn't
08:11even buy hand sanitizer in boots let alone at commercial suppliers. So I was mixing hand
08:16sanitizer in my lab and bringing that in and we were just trying to keep everybody safe because
08:21we knew we were crucial. The logistics were enormous and of course they were even harder
08:26during lockdown because we could not get supplies. We were phoning all over Europe to get thermometers
08:32to be able to measure the temperature of our volunteers because there were no thermometers
08:36that were available. We were short of supplies of PPE which we needed for our staff in the clinics.
08:41It was an absolute logistical nightmare.
08:54It is completely unimaginable and we're not at the peak yet.
08:59At the time I visited one of London's busiest intensive care units.
09:04So it's oxygen and organ support and amazing nursing care really.
09:11Witnessing the brutal reality of Covid.
09:16I've been in intensive care nursing for about 23 years now and I've never seen anything like this.
09:22The only real exit strategy was a vaccine but to find one that was safe and effective
09:28would require volunteers. We opened our database as an online database
09:34and had 10,000 people sign up within a matter of hours.
09:41The first doses were made here at the university's own biomanufacturing facility.
09:48The harmless modified virus which forms the vaccine was grown in a culture of adapted human
09:54cells. You just grow a little bit of the culture you take that and put it into a bigger culture
09:59and it grows you take that you put it into a bigger culture it grows. The end result was
10:03billions of particles of the modified virus. We keep the starting material at minus 80
10:09temperatures for long-term storage. This is the very first generation of the vaccine.
10:15It's made here in Oxford. After seven weeks there were enough doses to start the trial.
10:21My team were working around the clock so we just compressed everything and we didn't wait for the
10:27results of one stage before we went on to the next stage. So we took a risk with the project
10:31we still did the checks and if the checks had come back as a fail we'd have had to throw away
10:36the things we'd done but the only way to do it quickly was to just push straight through this to the end.
10:41We didn't have that vaccine ready to use until the day that we wanted to vaccinate people so it was
10:45One of the biggest steps for me and was monumental for me was the vaccination of the first individual
10:51and I remember walking home from the lab and almost breaking down because
10:56we'd got a vaccine and we got it into somebody's arm.
11:16Elisa Granato, a microbiologist, was the first person in Europe to be immunized on a Covid vaccine trial.
11:27I'm a scientist so of course I want to try and support science, the scientific process whenever
11:31I can and since I don't study viruses I felt a bit useless these days so I felt like this is a
11:37very easy way for me to support the cause. Yeah that's why I'm here and I'm excited.
11:41I'm just basically gonna sit here and incubate this thing and hopefully
11:47provide some good follow-up data and then we'll see and hopefully it works.
11:52Edward O'Neill, a cancer researcher, was also vaccinated that day. As a safety precaution the
11:59team waited 48 hours to check that Elisa and Edward had no serious adverse reactions.
12:05That's it.
12:09Both were well so the team immunized six more volunteers and gradually ramped up the numbers
12:15being vaccinated. I don't really feel nervous about it, I think it's been nice to get out of the house.
12:23The vaccine is created from an adenovirus, a type of virus that causes the common cold in
12:29chimpanzees, disabled so it can't cause an infection in humans. They insert a tiny fragment
12:37of genetic code, in this case from the coronavirus surface spike. When this modified cold virus is
12:43injected it breaks into human cells where the fragment of coronavirus genetic code that it
12:50contains program cells to make surface spikes that are identical to those found on coronavirus.
12:58The body's immune system learns to recognize these distinctive surface spikes
13:03so when the real coronavirus comes along the immune system is primed and ready.
13:13This was a randomized controlled trial so the volunteers were split into two.
13:19Half were testing the Covid vaccine, the others, the control group, were given a meningitis jab,
13:25chosen because this can also cause mild side effects. Neither volunteers nor scientists knew
13:31who was in which group. You're going to be randomized to get either the Covid-19 vaccine
13:37or the meningitis, you won't know what you are getting. We don't know if the Covid-19 vaccine
13:41is going to work so please don't assume any protection against Covid-19. So happy to continue?
13:46Yeah, lovely. Only a few days after receiving her vaccine there were shocking claims on social media
13:55that Elisa had died.
14:02It wasn't true. So a lot of work had to be done to for her sake as well as for the trial's sake
14:09to make it clear that this was just fake news. I spoke to her that day. Elisa, reports of your
14:17death have been greatly exaggerated, you're alive and well. I am indeed alive and well,
14:22thank you very much. I'm doing great, I feel absolutely fine. Any side effects so far? No,
14:28I feel absolutely great. I've never been better actually. I'm just out and about living my life.
14:33But while easy to disprove, it was just one of many conspiracy theories online.
14:39Waking up to think how malicious that can be, how people are really spreading
14:44nasty things about people and that doesn't feel fair because my team are all doing their best.
14:53In reality the trial was going well and by late May a thousand volunteers aged 18 to 55 had been enrolled.
15:04Among them were the Viney family, Tony, Katie and Rhiannon. I guess it was my idea. I saw it on
15:14Facebook and I sent the link to mum and dad and was like would you like to participate and they
15:18were like yeah. I wanted to do something that felt like we were helping in some way and thought well
15:24this is something that I can do. I travelled alone to my vaccine and it was when I pulled
15:30up in the car park I thought well it's now or never, you know, once you've done this there's
15:36no going back. But I walked in there bold as brass and felt great about it truthfully.
15:42They were asked to keep a note of any unusual symptoms. I had to fill in the e-diary for the
15:48first time and that was quite a long set of questions for the first seven days, asking
15:54of any fever, of any nausea, of any chills, of any... lots and lots and lots of questions
16:06and I had to answer no to every one of them because I just felt normal. It is just
16:11incomprehensible to think that the entire world has ground to a halt and if this vaccine is the
16:18way that we get out of this then, you know, that that is the biggest thing to hit all of us hopefully
16:25in our lifetimes. The team at Oxford had the goal of creating an affordable vaccine that could help
16:33the whole world but to do that they'd need billions of doses, something only a big pharmaceutical
16:39company could provide. The university was very clear that no profit should be made by anybody
16:45on our research during the pandemic period and that vaccines should be made available for low
16:49middle-income countries free of charge even after the pandemic. And of course that's a difficult one
16:54because that's not usually the way that big pharma works.
16:58They started negotiations with Mene Pangalos of the Cambridge-based pharmaceutical giant
17:04AstraZeneca. Obviously there were discussions about the not-for-profit, there were discussions
17:08about would we ever make a profit in the developed world, in the wealthy countries. You know, they
17:13weren't the only company that we had some early discussions with but when we started talking to
17:16AstraZeneca we realised they were also prepared to take the risk that it wasn't going to work
17:21because we could at the time, you know, we were in the middle of a pandemic, you know,
17:26because we couldn't work for the company who would just make enough vaccine for the clinical trials
17:33and wait and see if we got good efficacy before deciding whether to invest in manufacturing
17:39because that would be too slow. So we needed somebody who could take the financial risk.
17:44AstraZeneca was not an obvious choice. They only have one licensed vaccine.
17:51In terms of AstraZeneca, I mean, they're actually not known as a vaccine company.
17:57What was critical about AstraZeneca was that they, although they don't make many vaccines,
18:03they do have the networks that we need to tap into for the manufacturing around the world.
18:10AstraZeneca agreed not to make a profit from the vaccine during the pandemic and afterwards to sell
18:16it at cost price to low- and middle-income countries. In a huge vote of confidence,
18:22the government agreed to buy 100 million doses should the vaccine prove successful and provided
18:28nearly £90 million in support. The US government pledged 10 times that figure, partly to fund
18:36American trials.
18:51Four weeks after the first volunteers were immunized,
18:54Elisa and Edward returned for vital blood tests.
19:00If the vaccine was working, then by now their immune system should have developed
19:05a response to coronavirus detectable in their blood. Katie Ewer's team will analyze their
19:13samples. They're really the earliest indication we have that the vaccine might do something useful.
19:19So as soon as we've vaccinated people, we can start collecting those blood samples,
19:22testing for antibodies and T-cells, because we know if we've got those, then we have a chance.
19:26If the vaccine induces no immune response at all, then we have a serious problem and we probably
19:31need to go back to the drawing board.
19:37That's a lot of bottles.
19:45We're all curious to know. I mean, you must be curious to know...
19:49What's in there.
19:49What's in there.
19:50Yeah, pretty much.
19:51Are there the antibodies in there?
19:54We'll see.
19:54We'll see.
20:01A lot was riding on this. Failure now would have meant redesigning the vaccine.
20:07We need to begin processing within four hours of the sample being collected,
20:11because after that, those cells will start to die.
20:19This cellular detective work meant looking for clues as to whether the volunteers were
20:24building defences against coronavirus. Antibodies and T-cells are key parts of the
20:31immune system. Antibodies are the first line of defence. They stick to the surface spikes
20:37of coronavirus and neutralise them, preventing them from infecting cells.
20:44T-cells seek out those cells that have become infected and destroy them.
20:49Theresa Lamb's team looked for evidence of antibodies.
20:53We're very excited to have these samples in the lab today. We're very excited to see the redox.
21:00Yeah, all good.
21:01While Katie Ewers worked on T-cells. To do that required separating the blood
21:07by spinning it in a centrifuge.
21:11So, this is the blood sample. You can see we've got these different layers now.
21:15So, at the bottom here are the red blood cells, and here we've got this fuzzy white layer,
21:21and in this layer are the cells of the immune system. These are the T-cells that we're going
21:24to measure. Katie's postgrad student, Rebecca, removes the top layer. She then pipettes the
21:31white blood cell layer onto plates, which contain fragments of coronavirus. If the
21:37volunteers' immune systems have been stimulated by the vaccine, the immune system will be able
21:43to detect the virus. If the immune system has been stimulated by the vaccine, that will show
21:49up later as small spots on the plates. Each spot is like the footprint of a cell that's
21:57recognised the virus and made a response to it. We hope to see lots of spots in those
22:01ELISPOT wells, because that shows that the immune response is making lots of T-cells
22:05that can recognise the virus and clear it from the body. The samples are loaded into a machine,
22:12and the T-cells are created in each sample. Back in the olden days, when I started my PhD,
22:18we used to do this by hand with a magnifying lens, like an Inspector Clouseau magnifying
22:22glass, and you used to count them, and then you'd go to the next one and count that, yeah.
22:26Which is more accurate? This. Definitely this, yeah. Tired PhD students probably don't do the
22:34most accurate spot counting, I don't think. Many of the circles are covered with spots,
22:40and they're not quite as accurate as they used to be, but they're still quite accurate.
22:44It's great relief to see those immune responses. As immunologists, that's what we do day in,
22:47day out, and for a vaccine that was as important as this, the pressure is there even more to show
22:54a good response. The samples also showed evidence of antibodies. We were really happy, and we were
23:02really excited, because you see the results coming through as colour changes in a test,
23:08but you don't know whether those results are in the control or in a vaccinated individual,
23:13and it's only until we saw the results unblinded by our stats team did we really
23:18know that we had a vaccine that was inducing a strong immune response.
23:23It was an encouraging start, but these were just the blood results from the first volunteers.
23:28Much more data would be needed before they'd know if the vaccine really worked.
23:33By now, there were nearly a dozen coronavirus vaccines in human trials around the world.
23:40Among the leading contenders were vaccines from Pfizer-BioNTech and Moderna,
23:47part of an unprecedented scientific response to the pandemic.
23:53It's really important that we have a number of vaccines going forward, because there is not one
23:59vaccine that can do the whole world, and we need lots of them. So having two, three, four, five,
24:05the more the merrier. The Oxford team needed thousands more doses to expand their trials.
24:13We're only a small manufacturer. We only make a 10-litre culture, and from that we get about
24:18600 or so doses. So those doses were soon run out. So they ordered a batch to be manufactured
24:25in Italy. But when they tested it, they worried the vaccine levels were too concentrated.
24:33So to be on the safe side, and in agreement with the independent regulator,
24:37they injected volunteers with half the normal amount. But it turned out they'd been over-cautious.
24:45It was clear that the volunteers were having less immediate reactions. You know when you
24:51have a vaccination, you get swelling, sometimes a little bit of fever and elevated temperature.
24:57Clear that we were getting less of those when we were using this new batch of vaccine than we had
25:01been when we used our original batch of vaccine. More than a thousand participants had been
25:07inadvertently given a half dose. We immediately, when we found out, told the regulators.
25:15They understood the mistake and they said continue as we wanted to as well. It's actually
25:21a really good way of exploring two different dose regimens, a half dose full dose and a full dose.
25:27The regulators' agreement to keep this group in the trial would turn out to be highly significant.
25:34The trials grew to 19 sites across the UK. The clinical and scientific teams were busier than ever.
25:41Many of our scientists here at every level, from the most senior down to the most junior
25:47students, are working on this because there is just such a huge amount of work to do.
25:52I think now is a very exciting time to be working in vaccines.
25:56I've started doing malaria, Ebola, which are great diseases to be involved in and very interesting and very, very worthy of our time, but I've never worked on something that's been so close to home before.
26:09We've never vaccinated this many people in this scale of time and that's a huge challenge.
26:17We've been turning up to the lab to see what's going on, to see what's going on in the lab.
26:22We've been turning up to the lab at 8am and then we would be in there until one in the morning, two in the morning and then going home, going to bed, trying to sleep and going back and doing the exact same thing again.
26:36They were hours that I have never worked before in my life.
26:53By the start of summer, Covid infections here had fallen dramatically.
26:57While good news for most of us, it made things more difficult for the vaccine trial.
27:02It relied on volunteers being exposed to coronavirus in their daily lives in order to figure out if the vaccine was protecting them.
27:11It was clear that we were now taking a risk.
27:14Frontline health care workers were a priority for the trials.
27:18They faced a higher risk of coming into contact with the virus.
27:22In June, I visited Newcastle's Royal Victoria Hospital, where the vaccine trial was taking place.
27:29It was clear that we were now chasing the tail end of the first wave and there was a real risk that we wouldn't be able to get the answers that we'd hoped for really quickly.
27:39In June, I visited Newcastle's Royal Victoria Infirmary, where 500 NHS volunteers were immunised in a few days.
27:50So why did you sign up for the vaccine trial?
27:54Unfortunately, my dad fell ill with Covid and was admitted here for eight days.
27:59And I think once it's been that close to home, it makes more of a difference. You feel like you want to do your bit.
28:09One of the other volunteers that day was Veena, a consultant ophthalmologist.
28:15Some parts of the examination and the treatment involved getting very close to the patient.
28:22My concern was that the patients we treat are very vulnerable.
28:27Bright lights coming up.
28:29When I heard about the vaccine trials, you know, I thought this is something that, you know, we really need to grasp this chance with both hands.
28:39For a vaccine intended for global use, it was important to run international trials.
28:46I was extremely keen that we were testing in multiple different regions of the world,
28:51because it's important both for the generalisability of the vaccine, does it work in other places,
28:56but also to build confidence in different populations that the vaccine has been tested there.
29:02They targeted countries with high levels of infection.
29:07Brazil has the world's second largest outbreak behind the United States.
29:12The biggest city in the Amazon, where they're digging mass graves known as trenches.
29:16It's under control here in Brazil.
29:18The virus was spiralling out of control in Brazil.
29:22Soon, it would have the second highest death toll in the world.
29:26I was in Brazil when Professor Pollard called me and he was looking for a country to conduct the trials
29:34where he could prove quicker the efficacy and where we could do trials with quality and fast recruitment.
29:42We started initially with 2,000 subjects, then we increased to 5,000 subjects and finally 10,000 subjects.
29:50We started initially with 2,000 subjects, then we increased to 5,000 subjects and finally 10,000 subjects,
29:57which is just recruited.
30:00I really believe in what we are doing and especially with the high number of cases that we still have in Brazil,
30:06I believe that we can prove efficacy soon.
30:20Since the start of the trial back in April, the Oxford team had been testing samples from every volunteer,
30:26looking for signs of an immune response.
30:30On the 20th of July, they released their initial results.
30:36It was a slightly odd feeling, because quite often we publish these papers and
30:40we don't know what's going on.
30:45It was a slightly odd feeling, because quite often we publish these papers and
30:49some people in our field will be interested in them.
30:53I've never before been a co-author on a paper that has then had my phone buzzed with BBC breaking news.
30:57I've never before been a co-author on a paper that has then had my phone buzzed with BBC breaking news.
31:01Today at 6, scientists at Oxford reach a really important milestone in their work on a vaccine for coronavirus.
31:05Today at 6, scientists at Oxford reach a really important milestone in their work on a vaccine for coronavirus.
31:09It's safe, based on trials involving more than 1,000 people.
31:15We were able to show that both the antibodies were made which neutralised the virus
31:19and stop it infecting our cells, but also
31:23that we were inducing T-cells, which are absolutely critical
31:27for being able to fight the virus after it's already infected our cells.
31:31And so having those two components of the immune system
31:35working told us that we may well have a vaccine that could protect people.
31:43It was a good moment. It was clear that this vaccine was doing
31:47what it was meant to be doing. We have a vaccine that is
31:51generating a good immune response, it looks like it's well tolerated
31:55and this has a real chance of being a globally useful
31:59vaccine to curb the pandemic.
32:03Like most of those on the trial so far, the Vainis
32:07had been given just a single dose of vaccine.
32:11But a few who'd got a second dose showed a much stronger immune response.
32:15That meant asking volunteers to have a booster dose,
32:19sometimes months after their initial injection.
32:23We have the temperature,
32:27we'll have some blood and after we'll have the booster.
32:33But one dose or two, no one knew yet whether the immune response
32:37was strong enough to protect the volunteers
32:41from actually getting COVID-19.
32:45And up until this point, they'd only tested the vaccine
32:49on people aged between 18 and 55.
32:53For some vaccines, like the flu vaccine for example,
32:57older people don't make such a strong immune response and they don't get
33:01protection from the vaccine.
33:05Our plan initially was to vaccinate
33:09all the age groups at the same time, but we have an independent safety monitoring
33:13board and they thought we should be more conservative and do the younger people
33:17first and then move through to the older age groups, just to look at safety
33:21and monitor it as we went along.
33:25When the trial was finally opened up to older people,
33:29we met some of the over-70s recruited in Southampton.
33:45Among them, Helena and her husband David, both in their 80s.
34:07Is that it? That's it, all done, yeah.
34:11I know. I missed it. Blink and you miss it.
34:15Why did the two of you decide to come here today?
34:19We're very medical, our family. I was a doctor's daughter
34:23and we worked for the NHS obviously and we think anything we can do to help.
34:27The primary aim of the vaccine is to stop people
34:31getting ill. But if it could also prevent people getting
34:35infected at all, that would help stop transmission.
34:39So the volunteers are asked to do swab tests
34:43to pick up any who may have an infection, including those without
34:47symptoms.
34:51It's become a regular event for Helena and David.
34:57Another one done. David's making his box
35:01but I've made mine already. We do a weekly
35:05test which we have to send off in the post. We have to make sure we
35:09put the right sample in the right box.
35:13And if we can reduce both the symptomatic infection
35:17and the asymptomatic infection, that might mean that vaccines could
35:21have an impact on transmission. And that's a big deal
35:25because that means the virus could be stopped in its tracks.
35:37By the end of the summer, trials of the vaccine were running in six
35:41countries, including the UK, Brazil, South Africa
35:45and the United States. Nearly 20,000 volunteers
35:49had been recruited. But then, suddenly, everything
35:53stopped.
35:57Trials of a coronavirus vaccine being developed by the pharma giant
36:01AstraZeneca and Oxford University have been paused...
36:05A participant in that human trial has had a suspected adverse
36:09reaction. The trial is being developed with Oxford University...
36:13On the 6th of September, all the trials were halted after a participant
36:17developed a rare neurological condition. There was
36:21concern it might have been linked to the vaccine.
36:25When we start vaccinating large numbers of people, sometimes
36:29they will have what we call adverse events. It means anything bad
36:33that happens to them and we have to assess it. In a clinical trial of
36:37tens of thousands of people, stuff happens to people. People develop
36:41illnesses. There will be people who develop cancers and who develop neurological
36:45conditions. All these things happen in human populations.
36:49The difficulty in clinical trials is to work out whether it's
36:53associated with the intervention, the vaccine in our case, in the trial
36:57or not. An independent safety
37:01review said they couldn't find a link to the vaccine but couldn't
37:05rule it out either. The volunteer is now recovering
37:09and remains in the trial.
37:13Regulators in the UK, Brazil
37:17and South Africa allowed trials to resume within days.
37:21But it was six weeks before they restarted
37:25in the United States.
37:33All this was in the context of a vocal anti-vaccination
37:37movement.
37:41There is
37:45an anti-vaccine movement
37:49and what we would like to try to do is help people to understand
37:53how the vaccine works, how much work has gone into
37:57producing it. It's not something that we thought of in January and
38:01decided to give it a go. It builds on years and years of experience
38:05and understanding how to make vaccines in a safe way
38:09how to test vaccines in a safe way and what we need to do
38:13to get a vaccine that's going to protect people against this terrible disease.
38:17Nothing in life is 100% safe. There are risks associated with
38:21everything we do. There are risks with getting in a car,
38:25there are risks with drinking alcohol, there are risks with going on planes
38:29and it's the same when we take medicines. Paracetamol is not safe but we all take it.
38:33There are very tiny risks associated with all vaccines but we accept them
38:37and we accept that the risk of not being vaccinated is far, far greater.
38:49No clinical trials had ever had this kind of global attention.
38:53Scientists had become celebrities.
39:01How do you feel about being in the public eye?
39:05I would rather just get on with the science but it's important to
39:09explain the science to people. And what about all the media attention?
39:13It's been awful. Sorry.
39:17I can't say that to you can I but it's just not why we do it
39:21and we don't like it. There's cameras in your face.
39:25It's not something that we got into our career to do.
39:35The pressure has been pretty intense during the course of this year.
39:39I'd feel much better if I
39:43could get out and do some running and just clear the head and get
39:47away from it all, at least for an hour or two every now and then.
39:55Everyone is doing this because they're trying to do some good for the world
39:59and when you get a lot of the
40:03negative press and the criticism
40:07it's actually really, really tough and this has been for me
40:11probably the toughest thing I've ever worked on in terms of the goldfish bowl
40:15environment that you're in where every single thing
40:19is scrutinised, politicised, turned around,
40:23misrepresented.
40:27The virus is doubling
40:31faster than we can conceivably add capacity
40:35and so now is the time to take action because
40:39there is no alternative.
40:43By the beginning of November, COVID hospital admissions
40:47were rising as a second wave swept across much of the UK.
40:57The need for a vaccine
41:01was clearer than ever.
41:05We've actually got a vaccine being manufactured at the moment.
41:09Global production had begun and by now AstraZeneca had committed
41:13to three billion doses in 2021.
41:17That meant scaling up production at home and abroad,
41:21such as at this company, Oxford Biomedica, where they grow it
41:25in bioreactors.
41:29What we do is we then infect those cells with the viral seed stock of the vaccine.
41:33Once it's then produced it, we harvest it
41:37and start to purify it to remove all of the impurities.
41:41So this is like vaccine master chef then? All these people are playing a different
41:45role in growing this and creating it?
41:49They're all different chefs in there with all the specialities.
41:53AstraZeneca has also signed deals in Russia, Australia, Brazil
41:57and with India's Serum Institute,
42:01the world's biggest vaccine manufacturer.
42:05These will be essential for global access to the vaccine.
42:09The formula is the same
42:13worldwide. It was a team led by Sandy Douglas
42:17that worked out how to produce the vaccine at scale.
42:21It's a little bit like developing the recipe for Coke.
42:25So it takes quite a long time to get the recipe just right.
42:29But once you have that recipe, it's like a template and it can be transferred
42:33to all sorts of different manufacturing organisations around the world.
42:37And that's exactly what we've done.
42:41Some vaccines must be transported at ultra-low temperatures,
42:45but this one can be kept at around four degrees.
42:49Being able to store the vaccines in a fridge is game changing.
42:53If you have to store vaccines on dry ice
42:57at minus 80 degrees centigrade,
43:01that just brings additional challenges to how to get it into villages in the UK,
43:05let alone villages in sub-Saharan Africa and Brazil.
43:09And a vaccine that can be stored in a normal fridge,
43:13in my fridge here or anybody else's,
43:17and then given to a person, that changes everything.
43:21We've wanted to make as much of it as we possibly could
43:25and we've wanted to make sure that it's available in as many places as possible.
43:29And so we took some key strategic decisions
43:33early on to make sure that that would happen.
43:37By early November, trials of several vaccines,
43:41each involving tens of thousands of volunteers, were nearing completion.
43:45Scientists were anxiously waiting for independent data analysts
43:49to tell them when enough COVID cases had been accumulated
43:53to determine whether the vaccines offered any protection.
43:57I've worked in vaccines for long enough to know that
44:01most vaccines actually don't work.
44:05I've worked on clinical trials for malaria where we get no protection
44:09and it's the worst feeling in the world to have such high expectations
44:13and then to see nothing.
44:17So there's a mixture of anticipation but also tinged with a little bit of
44:21oh, I really hope it works.
44:25Could this be the moment the world has been waiting for?
44:29An effective vaccine against COVID-19.
44:33It's been developed by the US drugs company Pfizer
44:37and a German manufacturer BioNTech.
44:41It felt like a historic moment. We are winning this battle.
44:45That's my belief today.
44:49The first results were spectacular. Pfizer's vaccine had efficacy
44:53or trial effectiveness of nearly 95%.
44:57Moderna a week later announced the same astonishing levels of protection.
45:01I broke into an ear-to-ear grin when I heard the numbers.
45:05It really exceeded our best hopes.
45:09Do you think that life should be returning to normal by spring?
45:13Yes, yes, yes.
45:17Expectations were raised regarding what Oxford-AstraZeneca might deliver.
45:27And the following weekend, Andrew Pollard, the head of the global trials,
45:31was told the results.
45:35I was exhausted at that moment and went in
45:39and was very pleased to see that we had got efficacy of the vaccine.
45:45What was going to happen next was to try and start the disclosures
45:49which had to be to other colleagues here in Oxford, including Sarah,
45:53about the results.
45:57I was at home on a Saturday evening reading a book.
46:01We were in the middle of quarter-finals of MasterChef
46:05and the phone rang and I picked it up
46:09and it was my head of spiritual immunology who was calling me to tell me the results.
46:13And of course the first question is, has it worked?
46:17And the answer was, yes, we've got a vaccine.
46:21I was a little hazy because I hadn't expected to get that call at that time.
46:25And I pretty much stopped them
46:29and I just said, do we have efficacy or not?
46:33I was told yes and then the rest of it was a blur.
46:37The vaccine worked. The results showed it offered protection
46:41and was safe.
46:45Among more than 11,000 volunteers on the trial in the UK and Brazil,
46:49there were 101 cases of Covid in the control group
46:53and 30 in those that got the coronavirus vaccine.
46:57That's an overall protection of 70 per cent,
47:01better than most seasonal flu jabs.
47:05In the control group, 10 people were hospitalised with serious Covid and one died.
47:09In those that got the coronavirus vaccine,
47:13no one got seriously ill with Covid.
47:17It's very, very important that we made a vaccine that protects against severe disease.
47:21That's what vaccines should do and should achieve.
47:25The fact that nobody we vaccinated got severe disease is hugely important.
47:29The key point here is that it's a highly efficacious vaccine
47:33that is going to have a huge impact on the pandemic
47:37if we can get it licensed and then rolled out.
47:41The vaccine has key advantages over Pfizer and Moderna's.
47:45It doesn't need to be kept at minus 70 degrees
47:49and at £3 a dose, it's at least five times cheaper.
47:55Early Monday morning, the results were made public.
47:59Some news just in. Oxford University and the pharmaceutical firm AstraZeneca
48:03have published the preliminary results from large-scale trials
48:07of their coronavirus vaccine, showing that it's 70 per cent effective
48:11at preventing the disease.
48:15I was in bed in my pyjamas when I found out.
48:19I woke up to texts from friends and family congratulating me
48:23and saw that it had been released. I was absolutely over the moon.
48:27I was so happy. And then I had to swallow all my excitement
48:31and go off to work and do my shift.
48:35I was on the TV, my WhatsApp starts going off. Oh, my God, your vaccine's out!
48:39All my friends are like, yay! It was a good day, Monday.
48:43Got home, a colleague from college had left a magnum of English fizz
48:47in my porch, which I did not drink because I'm by myself
48:51and a magnum of fizz is too much for one person,
48:55even on the Monday that your vaccine's been proved efficacious.
48:59I was expecting the result to be in the format of, we have this number of cases
49:03and it's this level of efficacy, and it turned out not to be quite as simple.
49:07In fact, they ended up with three numbers.
49:11Overall efficacy was 70 per cent.
49:15Two full doses gave 62 per cent protection.
49:19Three volunteers given an initial half dose had 90 per cent protection,
49:23a result no-one had expected.
49:27Well, having three figures was a surprise and certainly complicates
49:31the story and the communication of it.
49:35I think, first of all, I thought, thank goodness it's working,
49:39and secondly, I was thinking, that's going to be quite difficult to explain.
49:43So how can an initial lower dose of vaccine deliver greater protection?
49:47The scientists themselves are still unsure.
49:51I didn't really understand exactly why we were seeing those results
49:55and I'm sure that was everybody else's reaction as well,
49:59but what really matters is understanding whether it's a real result
50:03and there are a number of other things in the trial that are internally consistent
50:07which tell us that this is a real result.
50:11But the complexity of the findings
50:15sparked criticism.
50:31Some felt the efficacy didn't compare well to Pfizer and Moderna.
50:35I'm not sure about you, Carolyn, but I think I'm going to be signing up
50:39for the 95 per cent efficacy vaccine rather than the maybe 70 per cent,
50:43maybe 60 per cent, maybe 90 per cent vaccine.
50:47Jennifer Rogers is an independent statistician who specialises
50:51in analysing clinical trial results.
50:55So when these results came out, we had three numbers, whereas in the other announcements
50:59we just had the one single number. I think that generated a bit of suspicion
51:03as to whether or not results were being cherry-picked.
51:07We also then found out that we had this low-dose, standard-dose mistake that happened.
51:11Then we found out that that had only happened in the 18 to 55 age group,
51:15so we didn't even know whether or not this worked in anybody over the age of 55.
51:19There just seemed to be these little mistakes
51:23and more and more got untangled as the days went on.
51:27Pfizer and Moderna, it was pretty simple and they did end up with just one result.
51:31Has part of the headache been because you've got
51:35partly different dosing but partly different countries
51:39and it's just made the whole thing more complex than one would have hoped for
51:43in an ideal world?
51:47I think there is no doubt that we would have run the study a little bit differently
51:51if we'd been doing it from scratch, but ultimately it is what it is.
51:55I think the Oxford group have done a fantastic job and then we've done as good a job as we possibly can
51:59to translate that into the data set that we can provide
52:03to the regulators and to regions around the world for the approval.
52:07In terms of the half dose, full dose, they were people who were 18 to 55
52:11that you got that 90% efficacy in.
52:15Is that potentially problematic because
52:19obviously the people you most want to protect are the over 65s
52:23and so you've only got that really high efficacy in a younger age group?
52:27Again, you're absolutely right that we have
52:31that efficacy signal in a younger age group. We've also shown
52:35in a different part of the study that the way that the patients
52:39respond to the vaccine are exactly the same
52:4318 to 55, 55 and above. So we actually haven't seen
52:47any difference in the way people respond to the vaccine by age.
52:51In the space of a year you've managed to come up with a vaccine, trial it
52:55and hopefully before the end of the year get it approved. Some people are going to say
52:59well, it's all gone a bit quick. How would you reassure people?
53:03It doesn't feel to me like it's been very quick. It seems to have taken about
53:0710 years to get to this point. But I think in the end
53:11the processes we've gone through are just the same and just as rigorous as in normal times.
53:15It's absolutely a key part of the reason
53:19why we do the trials is to establish the safety of the vaccines that we're testing.
53:23Why would people choose your vaccine
53:27not one that's better?
53:29Well we need all of the vaccines in order to have an impact in the pandemic.
53:33I think the key test for all of the vaccines is that they are used
53:37and that we start seeing a change in the pandemic. I don't think we should be
53:41looking at the numbers and trying to decide which one is better or the other.
53:45We need people vaccinated and that's got to happen soon if we want to get back to normal.
53:49Last week the Oxford team published
53:53an analysis of their trial data in a medical journal, The Lancet.
53:57This transparency has reassured experts.
54:01So now I think we are certain that they haven't cherry-picked
54:05the analyses and that will have been done in coordination with the regulators.
54:09We also know that this low standard dose
54:13yes it did happen as a mistake but was handled appropriately.
54:17The regulators were consulted at all times. I look at this data
54:21and I see a vaccine that shows all the promise of working.
54:25Oxford is really good at preventing severe coronavirus and there doesn't seem to be
54:29any safety concerns. I saw these results and I was positive.
54:33I think it's great news.
54:35It's really important to appreciate you don't necessarily need a 100%
54:39effective vaccine because if I'm vaccinated I protect myself
54:43and I hope to some degree I'm protecting others. It's not a competition between vaccines.
54:47We need multiple vaccines and we've got to have them at scale for the whole world.
54:51I would worry less about whether one is 60 or 70 and one is 80 or 90.
54:55I think they'll both be incredibly effective.
54:59The medical regulator, the MHRA, has been conducting
55:03a rolling review of the vaccine trials.
55:07It could decide within weeks whether to grant emergency approval
55:11and what dose should be given.
55:15But in the US, where a trial is still taking place,
55:19their regulator, the FDA, might take longer.
55:23Do they want to see those results of that trial in the US
55:27before they say yay or nay? Or could they just say yes, we've got
55:31a global pandemic here, give us your vaccine?
55:35We will take them through the data set but my
55:39assumption is that they will want to see the US data as well.
55:43So that might then mean waiting
55:47a few months. Weeks. We're recruiting a lot of people
55:51every day and event rates are pretty high in the US at the moment.
55:55We still don't know how effective the vaccine is in older people,
55:59how long protection lasts, or if it stops
56:03virus transmission. But for now, time to reflect.
56:07How does it feel to have got this far in this journey?
56:11It's a relief at this stage that all the work that people have done
56:15during the year and all the money that's been spent on manufacturing large amounts of this vaccine
56:19is not going to go to waste. It's quite a
56:23responsibility to say to people, you have to manufacture this vaccine now because
56:27we have to have a lot of doses ready to go. And we know it,
56:31we don't know if it works yet, but we can't wait, so get on with it.
56:35A vaccine that we have made, that went
56:39out into the world, is actually stopping people getting sick.
56:43It's a huge thing for us. I think we all had a little cry.
56:47It was worth it because we'd worked
56:51really hard. My son said something to me the other day that really impacted
56:55me and I was apologising for being late home
56:59for work again and he said, it's okay mummy, you're doing it for
57:03everybody, it's not just me you need to look after. And that
57:07did bring a tear to my eye. So what are you looking forward to
57:11in the future? You're going to make me emotional.
57:15I haven't seen my mum
57:19since last Christmas. Really? Yeah.
57:23She's in Greece and she's on her own.
57:27So that's tough. Yeah.
57:31It's been tough. It's been tough.
57:35Sorry, just take a moment.
57:39Sorry.
57:43Over the course of the year, it's been an emotional journey for everyone
57:47working on the Oxford AstraZeneca vaccine.
57:51Four million doses are ready to be handed over to the NHS.
57:55If approved, every adult in the country
57:59could be offered a jab next year.
58:03The government hopes by Easter, most over 65s and vulnerable
58:07a chance for life to finally return
58:11to normal. I think science has been the exit
58:15strategy for this pandemic and I think vaccines are at the heart of that scientific
58:19endeavour. And here we are with COVID, 10 months, 11 months into it
58:23and the scientific endeavour globally has produced those tools to
58:27bring the pandemic to a close.
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