WEBVTT - Covid Vaccine Front-Runner Ahead of Competition 0:00:00.120 --> 0:00:02.680 Hi, I'm Carol Masser and I'm Jason Kelly. It's time 0:00:02.680 --> 0:00:04.960 for this week's cover story. Well, of all the players 0:00:04.960 --> 0:00:08.440 developing a vaccine for COVID nineteen, here's a piece of advice. 0:00:08.480 --> 0:00:12.040 There's one name you should remember. Sarah Gilbert. That's right, Jason. 0:00:12.080 --> 0:00:14.680 The fifty eight year old University of Oxford professor is 0:00:14.840 --> 0:00:17.520 leading one of the most high profile and advanced vaccine 0:00:17.560 --> 0:00:21.360 candidates against COVID nineteen. The Oxford vaccine, a so called 0:00:21.480 --> 0:00:24.720 viral vector type, is already in phase three, or final 0:00:24.800 --> 0:00:28.040 stage trials. That puts Gilbert in her team months ahead 0:00:28.040 --> 0:00:31.560 of the competition. Oxford Well, it's also struck a deal 0:00:31.600 --> 0:00:35.960 with Astra Zeneca to spearhead global manufacturing and distribution. The 0:00:35.960 --> 0:00:39.320 pharma company has lined up agreements to produce two billion 0:00:39.400 --> 0:00:42.240 doses and sell the vaccine on a not for profit 0:00:42.280 --> 0:00:45.800 basis during the crisis. So why the impressive lead Because 0:00:45.840 --> 0:00:48.600 Gilbert's work on a vaccine for ebola and then mirrors 0:00:48.760 --> 0:00:52.760 another coronavirus gave her a running start when COVID nineteen emerged. 0:00:52.920 --> 0:00:56.440 While the big question remains the vaccines efficacy, Gilbert says 0:00:56.480 --> 0:01:00.360 she could have results by September the front on her. 0:01:00.920 --> 0:01:05.319 Oxford's COVID nineteen vaccine, devised by Sarah Gilbert, is in 0:01:05.440 --> 0:01:09.160 human trials. Astra Zenica has lined up agreements to produce 0:01:09.280 --> 0:01:15.199 two billion doses. Now the World waits. By Stephanie Baker. 0:01:17.640 --> 0:01:21.360 In April, Sarah Gilbert's three children, twenty one year old triplets, 0:01:21.360 --> 0:01:24.959 all studying biochemistry, decided to take part in a trial 0:01:25.040 --> 0:01:28.920 for an experimental vaccine against COVID nineteen. It was their 0:01:28.959 --> 0:01:32.480 mother's vaccine. She leads the University of Oxford team that 0:01:32.560 --> 0:01:36.160 developed it. But there wasn't a big family talk. We 0:01:36.200 --> 0:01:38.480 didn't really discuss it as I wasn't home much at 0:01:38.480 --> 0:01:42.039 the time. Gilbert told me recently. She'd been working around 0:01:42.080 --> 0:01:45.319 the clock, as one does while trying to end the pandemic, 0:01:45.760 --> 0:01:48.800 and at any rate, wasn't worried for her kids. We 0:01:48.920 --> 0:01:51.559 know the adverse event profile, and we know the dose 0:01:51.600 --> 0:01:54.240 to use because we've done this so many times before, 0:01:54.560 --> 0:01:58.320 she says. Obviously we're doing safety testing, but we're not 0:01:58.400 --> 0:02:03.080 concerned with safety. Low on her list of worries, her 0:02:03.120 --> 0:02:06.960 triplets are fine. Gilbert is focused on quickly determining how 0:02:07.000 --> 0:02:09.919 effective the vaccine will be and how it will be made. 0:02:10.560 --> 0:02:13.880 In April, Oxford struck a deal with British pharmaceutical giant 0:02:13.880 --> 0:02:18.200 astra Zenica to spearhead global manufacturing and distribution and help 0:02:18.280 --> 0:02:21.919 run more trials around the world. Astrazenica has agreed to 0:02:21.960 --> 0:02:24.280 sell the vaccine on a not for profit basis during 0:02:24.280 --> 0:02:27.360 the crisis if it proves effective, and has lined up 0:02:27.400 --> 0:02:31.240 deals with multiple manufacturers to produce more than two billion doses. 0:02:32.080 --> 0:02:35.000 Gilbert has been all over the British press, but she 0:02:35.040 --> 0:02:38.480 appears to regard public attention as a distraction. For more 0:02:38.520 --> 0:02:42.680 than two decades, she worked anonymously developing vaccines while also 0:02:42.840 --> 0:02:47.440 of necessity turning out endless grant applications. Her research was 0:02:47.520 --> 0:02:51.800 rarely discussed outside scientific circles. Now she's leading one of 0:02:51.800 --> 0:02:55.760 the most high profile and advanced vaccine candidates against COVID nineteen, 0:02:56.280 --> 0:03:00.560 with Phase three, or final stage trials under way involving 0:03:00.639 --> 0:03:04.320 thousands of people in Brazil, South Africa, the UK and 0:03:04.440 --> 0:03:09.320 soon the US. Money is no longer a struggle. At 0:03:09.320 --> 0:03:12.480 the end of April, crunching a process that normally takes 0:03:12.480 --> 0:03:16.000 about five years into less than four months, Gilbert and 0:03:16.040 --> 0:03:19.680 her colleagues at Oxford's Jenner Institute started a human trial 0:03:19.720 --> 0:03:24.160 on people. When Gilbert testified before a parliamentary committee in 0:03:24.240 --> 0:03:27.359 early July, one member compared her effort to going into 0:03:27.440 --> 0:03:30.960 a shed and coming out with the jet engine. Gilbert's 0:03:30.960 --> 0:03:34.000 team has leap frogged other vaccine contenders to the point 0:03:34.040 --> 0:03:36.880 where it will likely finish vaccinating subjects in its big 0:03:36.960 --> 0:03:40.880 ten thousand person efficacy trial before other candidates even start 0:03:40.960 --> 0:03:44.120 testing on that scale. Kate Bingham, chair of the UK 0:03:44.240 --> 0:03:47.400 government's Vaccine Task Force, told the committee in early July 0:03:48.280 --> 0:03:51.000 she's well ahead of the world. Bingham said it's the 0:03:51.080 --> 0:03:56.560 most advanced vaccine anywhere. Anthony Fauci, director of the u 0:03:56.680 --> 0:04:00.120 S National Institute of Allergy and Infectious Disease the in 0:04:00.240 --> 0:04:02.920 I a i D, has sounded a note of caution 0:04:02.960 --> 0:04:06.520 about Oxford's frontrunner status. You've got to be careful if 0:04:06.560 --> 0:04:09.880 you're temporarily leading the way versus having a vaccine that's 0:04:09.880 --> 0:04:13.520 actually going to work, he told the BBC. Recently, most 0:04:13.600 --> 0:04:17.279 vaccines in development failed to get licensed. Unlike drugs to 0:04:17.279 --> 0:04:21.320 treat diseases, vaccines are given to healthy people to prevent illness, 0:04:21.680 --> 0:04:24.760 which means regulators set a high bar for approval and 0:04:24.880 --> 0:04:28.039 usually want to see year's worth of safety data in 0:04:28.080 --> 0:04:31.520 the COVID nineteen pandemic. It's not yet clear what regulators 0:04:31.560 --> 0:04:34.560 will accept as proof of a successful and safe vaccine. 0:04:35.200 --> 0:04:37.839 The US Food and Drug Administration has said a vaccine 0:04:37.839 --> 0:04:40.960 would need to be more effective than a placebo to 0:04:41.040 --> 0:04:43.760 be approved, and would need to show more evidence than 0:04:43.800 --> 0:04:47.960 blood tests indicating an immune response. Regulators in other countries 0:04:48.040 --> 0:04:52.279 haven't spelled out what would be acceptable. Gilbert has voiced 0:04:52.320 --> 0:04:56.160 remarkable confidence in her chances, saying the Oxford vaccine has 0:04:56.160 --> 0:05:00.000 a probability of being effective in stopping people who are 0:05:00.040 --> 0:05:04.080 exposed to the novel coronavirus from developing COVID nineteen. She 0:05:04.240 --> 0:05:08.360 has said she could know by September. Asked by MPs 0:05:08.480 --> 0:05:10.839 in early July whether the world would have to struggle 0:05:10.839 --> 0:05:14.159 through the winter without a vaccine, Gilbert said, I hope 0:05:14.160 --> 0:05:20.919 we can improve on those timelines and come to your rescue. Gilbert, 0:05:21.040 --> 0:05:24.560 who is fifty eight, has the hyper efficient, serious demeanor 0:05:24.600 --> 0:05:26.760 you'd expect from someone who might be on the cusp 0:05:27.080 --> 0:05:30.159 of a breakthrough and hasn't a minute to spare. When 0:05:30.160 --> 0:05:33.120 I first called her in early March, she abruptly ended 0:05:33.120 --> 0:05:36.040 the conversation after ten minutes to speak to someone about 0:05:36.040 --> 0:05:39.400 the technical process of manufacturing the vaccine. It would have 0:05:39.440 --> 0:05:42.640 been crazy to take offense. Gilbert says. She wakes up 0:05:42.640 --> 0:05:45.120 at around four a m. Most days with lots of 0:05:45.200 --> 0:05:48.719 questions in my head, works from home for a few hours, 0:05:49.080 --> 0:05:52.000 then rides her bicycle to the institute, where she works 0:05:52.000 --> 0:05:55.320 into the evening. The Oxford team, just a handful of 0:05:55.360 --> 0:05:58.960 people in January, now comprises roughly two hundred and fifty. 0:06:00.080 --> 0:06:03.400 The vaccine is a so called viral vector type, based 0:06:03.400 --> 0:06:06.320 on years of research by Gilbert and Adrian Hill, the 0:06:06.360 --> 0:06:09.640 head of the Gender Institute. Traditional vaccines are made with 0:06:09.880 --> 0:06:12.760 a weekend or inactivated form of the germ that causes 0:06:12.800 --> 0:06:16.599 infection to stimulate an immune response. They aren't easy to 0:06:16.640 --> 0:06:20.400 develop and produce quickly. The Oxford team has created a 0:06:20.440 --> 0:06:23.760 technology that can speed the process by using a harmless 0:06:23.839 --> 0:06:26.240 virus as a kind of trojan horse to carry the 0:06:26.240 --> 0:06:29.480 genetic material of a pathogen into cells to generate an 0:06:29.480 --> 0:06:34.240 immune response. In the case of COVID nineteen, Gilbert has 0:06:34.279 --> 0:06:38.720 taken a chimpanzee adenavirus, a common cold virus, and inserted 0:06:38.760 --> 0:06:42.159 genetic material from the surface spike protein of the stars 0:06:42.240 --> 0:06:45.120 cove two virus as a way of tricking the immune 0:06:45.120 --> 0:06:49.280 system to fight back. The chimp adenavirus platform stimulates both 0:06:49.360 --> 0:06:53.200 antibodies and high levels of killer T cells, a type 0:06:53.200 --> 0:06:56.120 of white blood cell that helps the immune system destroy infection. 0:06:57.040 --> 0:07:00.800 Gilbert's approach is similar to a viral vector vaccine developed 0:07:00.839 --> 0:07:05.080 by the Chinese company Cancino Biologics that's in phase two 0:07:05.200 --> 0:07:08.960 human trials. The difference between the two is small, but 0:07:09.080 --> 0:07:13.040 maybe crucial. Cancino uses a vector based on a human 0:07:13.080 --> 0:07:17.480 adenovirus that many people have already been infected with. Early 0:07:17.600 --> 0:07:20.520 tests showed that people with pre existing antibodies to the 0:07:20.520 --> 0:07:24.120 adenavirus neutralized the vaccine before it could elicit a strong 0:07:24.160 --> 0:07:27.880 immune response to stars COVI two, the trojan horse is 0:07:27.920 --> 0:07:31.679 destroyed before the troops can get out. Johnson and Johnson 0:07:31.760 --> 0:07:35.240 is developing a similar vaccine based on a human adenovirus. 0:07:35.640 --> 0:07:38.160 It will begin human trials in the second half of July. 0:07:39.240 --> 0:07:43.880 A successful vaccine likely won't be effective no matter who 0:07:43.960 --> 0:07:47.760 wins the race, and success might have different definitions. Not 0:07:47.880 --> 0:07:51.640 all vaccines produce what's called sterilizing immunity, in which the 0:07:51.680 --> 0:07:54.960 body produces neutralizing antibodies that block of virus from getting 0:07:54.960 --> 0:07:59.160 into cells. Some vaccines don't prevent infection, but trigger the 0:07:59.160 --> 0:08:03.760 immune system to protect against illness. Jonas Salk's polio vaccine 0:08:03.880 --> 0:08:08.040 doesn't stop infection, but prevents the disease that crippled millions. 0:08:08.280 --> 0:08:11.520 I asked Gilbert what her definition of a successful vaccine 0:08:11.520 --> 0:08:14.320 would be, but she wouldn't be drawn out on specifics. 0:08:15.680 --> 0:08:18.080 We need a vaccine with a high level of efficacy 0:08:18.160 --> 0:08:22.280 against disease, which also has a significant impact on virus transmission, 0:08:22.480 --> 0:08:25.760 she said. The Oxford team probably wouldn't be so far 0:08:25.800 --> 0:08:28.560 along with its COVID vaccine had it not been for 0:08:28.640 --> 0:08:32.920 another deadly pathogen that threatened to cause a pandemic, Ebola. 0:08:33.080 --> 0:08:36.199 In fourteen, the Gender Institute led the first trial of 0:08:36.240 --> 0:08:40.240 an ebola vaccine devised by Glaxo smith Klein as part 0:08:40.240 --> 0:08:43.800 of the rapid response to an outbreak spreading through Guinea, Liberia, 0:08:43.840 --> 0:08:47.320 and Sierra Leone. The outbreak ended before they were able 0:08:47.360 --> 0:08:51.359 to finish. Merk got there first to test its experimental 0:08:51.440 --> 0:08:54.439 vaccine while cases were still spreading in Guinea. In twenty 0:08:54.559 --> 0:08:58.200 fifteen and one, regulatory approvals in the US and Europe 0:08:58.200 --> 0:09:01.240 at the end of last year. That experience taught the 0:09:01.280 --> 0:09:04.840 Oxford team about the importance of speed. We were horribly 0:09:04.880 --> 0:09:07.640 conscious the whole way through that one week, one way 0:09:07.760 --> 0:09:10.360 or the other might make a difference. Hill says it 0:09:10.480 --> 0:09:14.360 still might. In the wake of the Ebola outbreak, Gilbert 0:09:14.400 --> 0:09:17.160 responded to a call from the World Health Organization for 0:09:17.280 --> 0:09:20.400 researchers to come up with methods to rapidly respond to 0:09:20.520 --> 0:09:23.920 a clutch of emerging pathogens. It meant having a plan 0:09:24.000 --> 0:09:28.840 for disease X, that unknown yet inevitable pathogen lurking around 0:09:28.880 --> 0:09:32.640 the corner before COVID nineteen presented as the nightmare disease 0:09:32.800 --> 0:09:36.920 X scenario. Gilbert began working on Middle East Respiratory Syndrome 0:09:37.280 --> 0:09:41.240 or MIRRORS, another coronavirus that causes pneumonia and had threatened 0:09:41.240 --> 0:09:44.480 to spark a global health crisis. It first emerged in 0:09:44.520 --> 0:09:48.079 twelve in Saudi Arabia, but an outbreak didn't occur until 0:09:49.679 --> 0:09:53.120 MERS is much more deadly than COVID nineteen, killing about 0:09:53.120 --> 0:09:56.959 a third of those infected. Gilbert worked on a Mer's 0:09:57.040 --> 0:10:00.520 vaccine using the chimp adenavirus, in this case fused with 0:10:00.520 --> 0:10:03.680 the genetic material of the MIRRORS virus. She traveled to 0:10:03.679 --> 0:10:06.720 Saudi Arabia in November twenty fifteen for a conference with 0:10:06.800 --> 0:10:10.959 leading vaccinologists, hoping it would result in funding. It didn't. 0:10:11.559 --> 0:10:14.360 She and Hill had government grants to develop a number 0:10:14.400 --> 0:10:17.000 of vaccines, but that could take them only so far, 0:10:17.520 --> 0:10:21.280 and in twenty sixteen they created a private company called Vaxitech. 0:10:22.000 --> 0:10:24.679 It went on to raise more than thirty million pounds 0:10:25.000 --> 0:10:28.640 about thirty seven point eight million dollars from Google Ventures 0:10:28.920 --> 0:10:33.480 now g V, Sequoia Capital China, and Oxford Sciences Innovation, 0:10:33.880 --> 0:10:37.080 a venture capital funds set up to commercialize scientific research 0:10:37.160 --> 0:10:40.080 coming out of Oxford. The company holds the rights to 0:10:40.120 --> 0:10:44.560 several vaccines Gilbert and Hill are developing using the chimpadinavirus platform, 0:10:44.920 --> 0:10:50.360 including a promising prostate cancer therapy. The VC funding, along 0:10:50.400 --> 0:10:53.480 with some government money, helped them fine tune the viral 0:10:53.559 --> 0:10:56.640 vector program and pushed the Mirrors vaccine into a small 0:10:56.640 --> 0:11:00.679 safety trial with twenty four people in the Subjects were 0:11:00.679 --> 0:11:04.480 divided into three groups getting low, intermediate, and high doses. 0:11:04.920 --> 0:11:08.440 The results, published in April twenty twenty, showed the vaccine 0:11:08.440 --> 0:11:11.120 was safe and produced an immune response that persisted for 0:11:11.160 --> 0:11:14.560 a year. It produced high levels of T cells, but 0:11:14.640 --> 0:11:17.440 only forty four percent of people receiving the highest dose 0:11:17.760 --> 0:11:22.040 generated neutralizing antibodies. That raised the question of whether two 0:11:22.080 --> 0:11:26.000 doses might be needed. The Mirror's safety study couldn't prove 0:11:26.040 --> 0:11:29.240 whether the combination of T cells and neutralizing antibodies induced 0:11:29.280 --> 0:11:32.480 by the vaccine worked to prevent the disease because it 0:11:32.559 --> 0:11:35.320 was too small and took place in the UK, which 0:11:35.360 --> 0:11:38.600 has had only a handful of Mirr's cases since twenty twelve. 0:11:39.320 --> 0:11:42.320 In December twenty nineteen, just a few weeks before the 0:11:42.320 --> 0:11:46.280 novel coronavirus emerged in Wuhan, China, Gilbert's team began a 0:11:46.320 --> 0:11:49.360 second trial for the MERS vaccine in Saudi Arabia, where 0:11:49.400 --> 0:11:52.680 most of the world's cases have been reported. Even there, 0:11:52.720 --> 0:11:55.920 only about two hundred cases of MERS are reported annually, 0:11:56.280 --> 0:12:00.320 so proving the vaccine works could take many months. The 0:12:00.360 --> 0:12:03.839 work gave Gilbert a running start when COVID nineteen emerged. 0:12:04.240 --> 0:12:06.880 The spike protein of Mirr's shares a forty percent to 0:12:06.920 --> 0:12:09.960 fifty percent similarity to the spike of stars cove too, 0:12:10.080 --> 0:12:13.440 says Naive al Harby, a sawty scientist who studied under 0:12:13.440 --> 0:12:16.320 Gilbert at Oxford and is running the MIRRORS vaccine trials 0:12:16.320 --> 0:12:20.040 in Riad. We know the chimp adinavirus is safe in humans, 0:12:20.360 --> 0:12:22.920 and it's been tested in humans with the Mirr's spike. 0:12:23.440 --> 0:12:26.280 Given the similarities, the only question with the COVID nineteen 0:12:26.360 --> 0:12:28.920 vaccine is whether it's going to be protective or not. 0:12:30.320 --> 0:12:34.240 The Mirr's study was absolutely critical, says Tom Evans, chief 0:12:34.280 --> 0:12:38.040 scientific officer of Vaxateech. We could say, okay, we can 0:12:38.080 --> 0:12:41.200 start tomorrow. We don't have to make ten different varieties 0:12:41.240 --> 0:12:44.400 of this. We knew it could be manufactured, we knew 0:12:44.480 --> 0:12:50.600 it was immunogenic in humans. When she first heard about 0:12:50.640 --> 0:12:53.040 the cases of pneumonia in China over the new year, 0:12:53.400 --> 0:12:56.839 Gilbert was unsure how quickly it would spread. We didn't 0:12:56.840 --> 0:12:59.439 know what it was. Early on, she says. I was 0:12:59.480 --> 0:13:02.520 talking to colleagues, thinking, yeah, as soon as the sequence 0:13:02.559 --> 0:13:05.439 comes out, we'll make something. We'll test it in mice, 0:13:05.600 --> 0:13:08.400 we'll show what we can do. The moment the Chinese 0:13:08.440 --> 0:13:11.720 scientists published the genetic sequence of the novel coronavirus on 0:13:11.840 --> 0:13:16.160 January tenth, Gilbert got to work. Oxford had an advantage 0:13:16.240 --> 0:13:21.199 unusual for an academic institution, its own vaccine manufacturing facility, 0:13:21.679 --> 0:13:24.120 at which it was able to quickly manufacture the shot 0:13:24.200 --> 0:13:27.680 for the first phase of human trials. Gilbert arranged for 0:13:27.720 --> 0:13:31.440 the next larger batch to come from Italian farmer company Advent, 0:13:31.920 --> 0:13:34.880 and persuaded the university to underwrite the contract until she 0:13:34.880 --> 0:13:39.560 could secure further funding. On February, her team began injecting 0:13:39.559 --> 0:13:43.200 mice with a vaccine to accelerate a process that normally 0:13:43.240 --> 0:13:47.000 takes months. She was performing several steps at once, testing 0:13:47.000 --> 0:13:50.880 in animals, applying to regulators for human trials, and talking 0:13:50.880 --> 0:13:55.720 to manufacturers. Her level of knowledge of the detail is extraordinary, 0:13:55.760 --> 0:13:58.600 says Andrew McLean, who worked with her for years as 0:13:58.640 --> 0:14:01.520 an investor and board member at VACKS attack. It's very 0:14:01.600 --> 0:14:04.240 unusual for a scientist to know the practical parts of 0:14:04.240 --> 0:14:06.360 getting a drug made and be able to talk to 0:14:06.440 --> 0:14:10.480 manufacturers on a toe to toe basis. But in early 0:14:10.559 --> 0:14:13.880 March Gilbert was still scrounging for money. She got a 0:14:13.880 --> 0:14:17.559 small grant from the Coalition for Epidemic Preparedness Innovations or 0:14:17.679 --> 0:14:20.360 c e p I, a foundation set up in twenty 0:14:20.440 --> 0:14:23.360 seventeen with funding from the Bill and Melinda Gates Foundation, 0:14:23.720 --> 0:14:26.760 the governments of Norway in India, and the Welcome Trust, 0:14:27.000 --> 0:14:29.800 a research charity based in London. It was enough to 0:14:29.880 --> 0:14:33.000 keep them going Around this time, there was a debate 0:14:33.080 --> 0:14:35.880 within the Gender Institute about whether to go straight into 0:14:35.960 --> 0:14:38.400 human trials or wait until they got results from a 0:14:38.440 --> 0:14:41.400 study of their vaccine in nine REESUS monkeys at the 0:14:41.480 --> 0:14:44.560 Rocky Mountain Laboratories in Montana, part of the n I 0:14:44.720 --> 0:14:47.560 A I D. They knew that in tests for a 0:14:47.640 --> 0:14:51.160 vaccine against the first Stars virus, which caused an epidemic 0:14:51.160 --> 0:14:54.240 in Asia in two thousand two and three, some vaccinated 0:14:54.280 --> 0:14:57.400 animals became more severely ill after they were challenged with 0:14:57.440 --> 0:15:02.160 the virus than unvaccinated ones did. The phenomenon is known 0:15:02.200 --> 0:15:06.920 as antibody dependent enhancement or a d E. Scientists around 0:15:06.920 --> 0:15:09.240 the world were worried that might happen again with the 0:15:09.320 --> 0:15:12.680 Stars Cove two vaccine, and the Oxford team wanted to 0:15:12.720 --> 0:15:15.600 test it in monkeys to rule it out, but time 0:15:15.640 --> 0:15:18.680 was of the essence. People were dying from COVID nineteen 0:15:19.120 --> 0:15:22.240 and waiting for the monkey results would mean losing crucial weeks. 0:15:23.080 --> 0:15:25.960 We were doing that monkey experiment for safety and to 0:15:26.000 --> 0:15:28.440 convince the pessimists that the vaccine was going to be 0:15:28.480 --> 0:15:32.360 safe after infection. Hill says, the big question was when 0:15:32.360 --> 0:15:34.800 you have a vaccine available, and you have people lined 0:15:34.840 --> 0:15:37.200 up ready to go. Do you wait for the monkey 0:15:37.200 --> 0:15:41.160 results to vaccinate them? They decided to play it safe 0:15:41.200 --> 0:15:44.520 and wait, while pressing ahead with planning the trials, setting 0:15:44.600 --> 0:15:48.640 up manufacturing, and looking for more money. On March twenty third, 0:15:48.960 --> 0:15:51.840 the same day UK Prime Minister Boris Johnson ordered the 0:15:51.840 --> 0:15:54.960 country into lockdown, the government announced a two point two 0:15:55.000 --> 0:15:59.400 million pound grant to Gilbert's team to support testing and manufacturing. 0:16:00.200 --> 0:16:03.000 During the search for money, Bill Gates pushed Gilbert and 0:16:03.080 --> 0:16:06.120 Hill to partner with a big pharmaceutical company, and as 0:16:06.160 --> 0:16:10.040 a C E p I founder, he had leverage. We 0:16:10.120 --> 0:16:13.000 went to Oxford and said, you are doing brilliant work, 0:16:13.200 --> 0:16:16.040 Gates recalled in a call with reporters in early June. 0:16:16.800 --> 0:16:19.120 You really need to team up, and we told them 0:16:19.160 --> 0:16:21.680 a list of people to go and talk to. The 0:16:21.720 --> 0:16:25.360 Oxford team was initially reluctant, Hill says, because they'd run 0:16:25.360 --> 0:16:28.520 plenty of trials on their own. What we struggle against 0:16:28.600 --> 0:16:30.920 all the time is the perception from fonders that we 0:16:31.000 --> 0:16:34.240 can't do this, he says. They held talks with several 0:16:34.240 --> 0:16:38.280 potential partners, whom he declined to name, asking them two questions, 0:16:38.640 --> 0:16:42.040 how much can you manufacture and by when? They didn't 0:16:42.040 --> 0:16:44.680 answer either of those questions, no matter how many times 0:16:44.720 --> 0:16:49.960 we asked, Hill recalls astra Zenica was different. In early April, 0:16:50.080 --> 0:16:54.280 Minne Pangalos, the company's head of research and development for biopharmaceuticals, 0:16:54.560 --> 0:16:58.240 had been hearing positive things about Oxford's work. Although astra 0:16:58.280 --> 0:17:01.520 Zenica isn't a big player in back scenes. It produces 0:17:01.520 --> 0:17:04.760 a nasal flu spray vaccine, but nothing else. He thought 0:17:04.800 --> 0:17:08.320 it was worth calling John Bell, an immunologist and professor 0:17:08.359 --> 0:17:11.960 who directs the university's medical research strategy, to find out more. 0:17:12.800 --> 0:17:16.159 It seemed like they needed a partner, Pangalos recalls. I 0:17:16.240 --> 0:17:18.800 called John up and said, are you interested in working 0:17:18.880 --> 0:17:21.040 with us on this because we think we can help. 0:17:22.040 --> 0:17:25.480 Pangalos negotiated the partnership agreement with Bell and the rest 0:17:25.480 --> 0:17:27.879 of the Oxford team in about ten days through a 0:17:27.880 --> 0:17:31.800 flurry of zoom calls, with Gilbert walking everyone through the data. 0:17:32.280 --> 0:17:36.359 Astra Zeneca agreed to be responsible for worldwide distribution and manufacturing. 0:17:37.440 --> 0:17:39.760 Big money followed the announcement of the deal at the 0:17:39.840 --> 0:17:43.560 end of April. As Pascal Sorrio, astra Zeneca's chief executive 0:17:43.600 --> 0:17:46.399 officer pledged to make the vaccine available at only a 0:17:46.440 --> 0:17:50.280 few dollars per dose. The British government gave sixty five 0:17:50.320 --> 0:17:53.760 million pounds to accelerate the work and order thirty million 0:17:53.760 --> 0:17:56.439 doses for the UK by September, as part of a 0:17:56.480 --> 0:17:59.560 deal to make one million in total, with some reserve 0:17:59.640 --> 0:18:03.680 for de heloping countries. Days later, astra Zeneca announced a 0:18:03.760 --> 0:18:06.000 one point to billion dollar deal with the U s 0:18:06.080 --> 0:18:10.560 Biomedical Advanced Research and Development Authority BARDA to develop and 0:18:10.560 --> 0:18:14.520 produce three hundred million doses, one of the largest deals 0:18:14.520 --> 0:18:17.879 the agency has announced. Astra Zeneca will work with the 0:18:17.960 --> 0:18:20.760 National Institutes of Health to test it in thirty thousand 0:18:20.840 --> 0:18:24.480 people in the US, scheduled to start in August. The 0:18:24.520 --> 0:18:27.560 company later struck a licensing deal with the Serum Institute 0:18:27.560 --> 0:18:30.639 of India to produce a billion doses for developing and 0:18:30.680 --> 0:18:35.600 middle income countries. Because of expected political pressure, any country 0:18:35.640 --> 0:18:37.960 with a role in the production of a vaccine might 0:18:38.000 --> 0:18:41.240 act to secure doses for its own people. Astra Zeneca 0:18:41.400 --> 0:18:44.600 is setting up independent supply chains within countries to prevent 0:18:44.640 --> 0:18:48.760 delays at national borders. As the astro Zenica deal was 0:18:48.800 --> 0:18:51.639 being finalized in mid April, the results of the monkey 0:18:51.640 --> 0:18:56.600 study came through from Montana. It wasn't promising, it was fantastic. 0:18:56.800 --> 0:19:00.239 Hill says. Not only were the monkeys fine, it as 0:19:00.240 --> 0:19:03.880 a bonus we saw some protection. They had vaccinated six 0:19:03.920 --> 0:19:06.879 monkeys and then twenty eight days later, exposed them to 0:19:06.960 --> 0:19:12.399 a massive dose of stars COVID two via multiple roots, eyes, mouth, nose, 0:19:12.480 --> 0:19:16.000 and trachea to expose the lungs. It was much more 0:19:16.040 --> 0:19:19.240 than a person might encounter on public transportation or even 0:19:19.280 --> 0:19:22.760 in a COVID Ward after exposure, the animals showed no 0:19:22.920 --> 0:19:26.160 signs of pneumonia in their lungs by all indications, They 0:19:26.160 --> 0:19:30.600 felt fine. Nasal swabs, however, showed they still had the virus, 0:19:30.920 --> 0:19:35.000 meaning they might be able to infect others. The study's 0:19:35.040 --> 0:19:38.320 aim was to determine safety, not efficacy, so the gender 0:19:38.320 --> 0:19:40.840 team was encouraged to see it provided some protection in 0:19:40.880 --> 0:19:43.920 the face of an overwhelming dose of the virus. The 0:19:44.040 --> 0:19:47.320 day after the preliminary results came in, a team headed 0:19:47.320 --> 0:19:50.560 by Andrew Pollard, a colleague of Gilbert's, running the clinical trials, 0:19:50.840 --> 0:19:54.919 started injecting people. When the full results of the monkey 0:19:54.920 --> 0:19:58.480 trials were published in mid May, critics pounced seeing the 0:19:58.520 --> 0:20:02.520 results as weak. William Hazeltine, a former professor at Harvard 0:20:02.520 --> 0:20:06.200 Medical School who spent years researching HIV, wrote a piece 0:20:06.200 --> 0:20:08.919 in Forbes arguing that the Oxford vaccine looked like it 0:20:08.960 --> 0:20:12.400 would be only partially protective because it didn't generate high 0:20:12.480 --> 0:20:17.040 levels of neutralizing antibodies, which defends cells against infection. What 0:20:17.160 --> 0:20:19.600 happens when you have a vaccine with people running around 0:20:19.600 --> 0:20:22.720 with virus spewing out of their nose. Anyone who is 0:20:22.760 --> 0:20:26.320 not vaccinated or not vaccinated well is going to get infected, 0:20:26.640 --> 0:20:30.639 Hazeltine told me on a zoom call. My guess is 0:20:30.680 --> 0:20:33.199 the Oxford vaccine isn't going to be powerful enough for 0:20:33.240 --> 0:20:35.600 older people, so they will have to boost it up, 0:20:35.680 --> 0:20:39.560 and boosting it up can have side effects. On July fourteenth, 0:20:39.600 --> 0:20:42.040 the U. S. Government released results from the safety trial 0:20:42.320 --> 0:20:46.600 of another vaccine candidate from Maderna. The company's stock rose 0:20:46.720 --> 0:20:49.960 sharply on news that the vaccine produced neutralizing antibodies in 0:20:50.000 --> 0:20:55.520 all patients. It also produced side effects in some Maderna's vaccine, 0:20:55.560 --> 0:20:59.040 produced using a technique called Messenger RNA, will go into 0:20:59.119 --> 0:21:03.119 late stage trials by the end of July. Team Oxford 0:21:03.160 --> 0:21:06.760 Astra Zeneca argues it's not realistic to expect clear nasal 0:21:06.800 --> 0:21:09.720 swabs from monkeys after they got a whopping dose straight 0:21:09.800 --> 0:21:12.720 up their noses. It doesn't need to cure you of 0:21:12.760 --> 0:21:16.800 stars cove too. Astra Zeneca's Pungalow says, I don't know 0:21:16.840 --> 0:21:20.520 if we will completely knock out shedding or people being infectious, 0:21:20.520 --> 0:21:22.960 whether we're going to cure people completely, or whether we 0:21:22.960 --> 0:21:26.120 will just dampen down the illness. We want a vaccine 0:21:26.119 --> 0:21:28.960 to stop people from going to hospital and dying. If 0:21:29.000 --> 0:21:32.080 you can do that, I think people will be pretty happy. 0:21:32.320 --> 0:21:34.760 Neutralizing antibodies is one of the things you'll look at, 0:21:35.119 --> 0:21:37.360 but the T cell response is going to be important. 0:21:38.640 --> 0:21:42.119 Hill says the same thing. Has Alten's focus on neutralizing 0:21:42.160 --> 0:21:46.359 antibodies is misplaced scientific debates aside. I was starting to 0:21:46.400 --> 0:21:51.000 sense a Harvard Oxford American British rivalry playing out. It's 0:21:51.040 --> 0:21:54.359 simpler to measure antibodies, it's less expensive. People do it 0:21:54.400 --> 0:21:57.360 all the time, But often the antibodies are a surrogate 0:21:57.400 --> 0:22:01.399 for the T cell number. Hill says, nobody knows in SARS, 0:22:01.400 --> 0:22:04.720 in mers and in COVID nineteen the relative importance of 0:22:04.720 --> 0:22:08.320 those two A flurry of recent research has shown that 0:22:08.359 --> 0:22:11.320 T cells may play an important role in responses to 0:22:11.359 --> 0:22:14.119 SARS cove two, but the only way to know the 0:22:14.119 --> 0:22:17.720 most effective levels or tighters of antibodies and T cells 0:22:17.800 --> 0:22:20.119 is to test the vaccine in people where the virus 0:22:20.160 --> 0:22:24.320 is circulating. No one knows how strong the immune response 0:22:24.359 --> 0:22:27.200 needs to be to achieve protection in people of any age. 0:22:27.240 --> 0:22:30.480 Gilbert says, if we get a strong T cell response, 0:22:30.800 --> 0:22:33.639 we don't need such a high neutralizing antibody tighter to 0:22:33.720 --> 0:22:37.040 achieve protection. The two arms of the immune response work 0:22:37.119 --> 0:22:41.000 together to give better protection. The Gender Institute team is 0:22:41.080 --> 0:22:43.600 taking blood samples of people in the trials that begin 0:22:43.600 --> 0:22:46.240 in late April and May in the UK to measure 0:22:46.280 --> 0:22:50.359 antibodies and T cell responses several weeks after vaccination, but 0:22:50.480 --> 0:22:53.920 blood results can't prove it will prevent disease. It's a 0:22:54.000 --> 0:22:57.240 numbers game. They're looking for very few cases of COVID 0:22:57.320 --> 0:23:00.240 nineteen in people who have received the vaccine, and a 0:23:00.240 --> 0:23:03.280 significantly higher number in a control group of people who haven't. 0:23:03.880 --> 0:23:06.840 The better the vaccine is, the quicker you get a result, 0:23:07.119 --> 0:23:10.120 and the smaller number you need. Hill says, if they 0:23:10.160 --> 0:23:13.760 reach say twenty cases in the control group and eighteen 0:23:13.800 --> 0:23:17.240 among the vaccinated cohort. That's not a great vaccine, and 0:23:17.280 --> 0:23:19.480 they would need a lot of cases to show a difference. 0:23:20.000 --> 0:23:22.040 But if you have twenty in the control group and 0:23:22.160 --> 0:23:25.840 two among the vaccinated, your home and dry, he says. 0:23:26.960 --> 0:23:29.040 Of course, a quicker way of figuring out if it 0:23:29.080 --> 0:23:32.080 works would be to stage human challenge trials like those 0:23:32.119 --> 0:23:35.680 done with the monkeys. So far, no COVID nineteen vaccine 0:23:35.720 --> 0:23:39.320 developer has used to challenge trials because of ethical concerns 0:23:39.359 --> 0:23:41.520