Covid Vaccine Front-Runner Ahead of Competition

stage trials. That puts Gilbert in her team months ahead of the competition. Oxford Well, it's also struck a deal with Astra Zeneca to spearhead global manufacturing and distribution. The pharma company has lined up agreements to produce two billion doses and sell the vaccine on a not for profit basis during the crisis. So why the impressive lead Because Gilbert's work on a vaccine for ebola and then mirrors another coronavirus gave her a running start when COVID nineteen emerged.

While the big question remains the vaccines efficacy, Gilbert says she could have results by September the front on her. Oxford's COVID nineteen vaccine, devised by Sarah Gilbert, is in human trials. Astra Zenica has lined up agreements to produce two billion doses. Now the World waits. By Stephanie Baker. In April, Sarah Gilbert's three children, twenty one year old triplets, all studying biochemistry, decided to take part in a trial

for an experimental vaccine against COVID nineteen. It was their mother's vaccine. She leads the University of Oxford team that developed it. But there wasn't a big family talk. We didn't really discuss it as I wasn't home much at the time. Gilbert told me recently. She'd been working around the clock, as one does while trying to end the pandemic,

and at any rate, wasn't worried for her kids. We know the adverse event profile, and we know the dose to use because we've done this so many times before, she says. Obviously we're doing safety testing, but we're not concerned with safety. Low on her list of worries, her triplets are fine. Gilbert is focused on quickly determining how effective the vaccine will be and how it will be made.

In April, Oxford struck a deal with British pharmaceutical giant astra Zenica to spearhead global manufacturing and distribution and help run more trials around the world. Astrazenica has agreed to sell the vaccine on a not for profit basis during the crisis if it proves effective, and has lined up deals with multiple manufacturers to produce more than two billion doses. Gilbert has been all over the British press, but she

appears to regard public attention as a distraction. For more than two decades, she worked anonymously developing vaccines while also of necessity turning out endless grant applications. Her research was rarely discussed outside scientific circles. Now she's leading one of the most high profile and advanced vaccine candidates against COVID nineteen, with Phase three, or final stage trials under way involving thousands of people in Brazil, South Africa, the UK and

soon the US. Money is no longer a struggle. At the end of April, crunching a process that normally takes about five years into less than four months, Gilbert and her colleagues at Oxford's Jenner Institute started a human trial on people. When Gilbert testified before a parliamentary committee in early July, one member compared her effort to going into

a shed and coming out with the jet engine. Gilbert's team has leap frogged other vaccine contenders to the point where it will likely finish vaccinating subjects in its big ten thousand person efficacy trial before other candidates even start testing on that scale. Kate Bingham, chair of the UK government's Vaccine Task Force, told the committee in early July she's well ahead of the world. Bingham said it's the

most advanced vaccine anywhere. Anthony Fauci, director of the u S National Institute of Allergy and Infectious Disease the in I a i D, has sounded a note of caution about Oxford's frontrunner status. You've got to be careful if you're temporarily leading the way versus having a vaccine that's actually going to work, he told the BBC. Recently, most

vaccines in development failed to get licensed. Unlike drugs to treat diseases, vaccines are given to healthy people to prevent illness, which means regulators set a high bar for approval and usually want to see year's worth of safety data in the COVID nineteen pandemic. It's not yet clear what regulators will accept as proof of a successful and safe vaccine.

The US Food and Drug Administration has said a vaccine would need to be more effective than a placebo to be approved, and would need to show more evidence than blood tests indicating an immune response. Regulators in other countries haven't spelled out what would be acceptable. Gilbert has voiced remarkable confidence in her chances, saying the Oxford vaccine has a probability of being effective in stopping people who are exposed to the novel coronavirus from developing COVID nineteen. She

has said she could know by September. Asked by MPs in early July whether the world would have to struggle through the winter without a vaccine, Gilbert said, I hope we can improve on those timelines and come to your rescue. Gilbert, who is fifty eight, has the hyper efficient, serious demeanor you'd expect from someone who might be on the cusp

of a breakthrough and hasn't a minute to spare. When I first called her in early March, she abruptly ended the conversation after ten minutes to speak to someone about the technical process of manufacturing the vaccine. It would have been crazy to take offense. Gilbert says. She wakes up at around four a m. Most days with lots of questions in my head, works from home for a few hours, then rides her bicycle to the institute, where she works

into the evening. The Oxford team, just a handful of people in January, now comprises roughly two hundred and fifty. The vaccine is a so called viral vector type, based on years of research by Gilbert and Adrian Hill, the head of the Gender Institute. Traditional vaccines are made with a weekend or inactivated form of the germ that causes infection to stimulate an immune response. They aren't easy to

develop and produce quickly. The Oxford team has created a technology that can speed the process by using a harmless virus as a kind of trojan horse to carry the genetic material of a pathogen into cells to generate an immune response. In the case of COVID nineteen, Gilbert has taken a chimpanzee adenavirus, a common cold virus, and inserted genetic material from the surface spike protein of the stars cove two virus as a way of tricking the immune

system to fight back. The chimp adenavirus platform stimulates both antibodies and high levels of killer T cells, a type of white blood cell that helps the immune system destroy infection. Gilbert's approach is similar to a viral vector vaccine developed by the Chinese company Cancino Biologics that's in phase two human trials. The difference between the two is small, but maybe crucial. Cancino uses a vector based on a human

adenovirus that many people have already been infected with. Early tests showed that people with pre existing antibodies to the adenavirus neutralized the vaccine before it could elicit a strong immune response to stars COVI two, the trojan horse is destroyed before the troops can get out. Johnson and Johnson is developing a similar vaccine based on a human adenovirus. It will begin human trials in the second half of July. A successful vaccine likely won't be effective no matter who

wins the race, and success might have different definitions. Not all vaccines produce what's called sterilizing immunity, in which the body produces neutralizing antibodies that block of virus from getting into cells. Some vaccines don't prevent infection, but trigger the immune system to protect against illness. Jonas Salk's polio vaccine doesn't stop infection, but prevents the disease that crippled millions.

I asked Gilbert what her definition of a successful vaccine would be, but she wouldn't be drawn out on specifics. We need a vaccine with a high level of efficacy against disease, which also has a significant impact on virus transmission, she said. The Oxford team probably wouldn't be so far along with its COVID vaccine had it not been for another deadly pathogen that threatened to cause a pandemic, Ebola.

In fourteen, the Gender Institute led the first trial of an ebola vaccine devised by Glaxo smith Klein as part of the rapid response to an outbreak spreading through Guinea, Liberia, and Sierra Leone. The outbreak ended before they were able to finish. Merk got there first to test its experimental vaccine while cases were still spreading in Guinea. In twenty fifteen and one, regulatory approvals in the US and Europe at the end of last year. That experience taught the

Oxford team about the importance of speed. We were horribly conscious the whole way through that one week, one way or the other might make a difference. Hill says it still might. In the wake of the Ebola outbreak, Gilbert responded to a call from the World Health Organization for researchers to come up with methods to rapidly respond to

a clutch of emerging pathogens. It meant having a plan for disease X, that unknown yet inevitable pathogen lurking around the corner before COVID nineteen presented as the nightmare disease X scenario. Gilbert began working on Middle East Respiratory Syndrome or MIRRORS, another coronavirus that causes pneumonia and had threatened

to spark a global health crisis. It first emerged in twelve in Saudi Arabia, but an outbreak didn't occur until MERS is much more deadly than COVID nineteen, killing about a third of those infected. Gilbert worked on a Mer's vaccine using the chimp adenavirus, in this case fused with the genetic material of the MIRRORS virus. She traveled to Saudi Arabia in November twenty fifteen for a conference with leading vaccinologists, hoping it would result in funding. It didn't.

She and Hill had government grants to develop a number of vaccines, but that could take them only so far, and in twenty sixteen they created a private company called Vaxitech. It went on to raise more than thirty million pounds about thirty seven point eight million dollars from Google Ventures now g V, Sequoia Capital China, and Oxford Sciences Innovation, a venture capital funds set up to commercialize scientific research

coming out of Oxford. The company holds the rights to several vaccines Gilbert and Hill are developing using the chimpadinavirus platform, including a promising prostate cancer therapy. The VC funding, along with some government money, helped them fine tune the viral vector program and pushed the Mirrors vaccine into a small safety trial with twenty four people in the Subjects were divided into three groups getting low, intermediate, and high doses.

The results, published in April twenty twenty, showed the vaccine was safe and produced an immune response that persisted for a year. It produced high levels of T cells, but only forty four percent of people receiving the highest dose generated neutralizing antibodies. That raised the question of whether two

doses might be needed. The Mirror's safety study couldn't prove whether the combination of T cells and neutralizing antibodies induced by the vaccine worked to prevent the disease because it was too small and took place in the UK, which has had only a handful of Mirr's cases since twenty twelve. In December twenty nineteen, just a few weeks before the novel coronavirus emerged in Wuhan, China, Gilbert's team began a second trial for the MERS vaccine in Saudi Arabia, where

most of the world's cases have been reported. Even there, only about two hundred cases of MERS are reported annually, so proving the vaccine works could take many months. The work gave Gilbert a running start when COVID nineteen emerged. The spike protein of Mirr's shares a forty percent to fifty percent similarity to the spike of stars cove too, says Naive al Harby, a sawty scientist who studied under Gilbert at Oxford and is running the MIRRORS vaccine trials

in Riad. We know the chimp adinavirus is safe in humans, and it's been tested in humans with the Mirr's spike. Given the similarities, the only question with the COVID nineteen vaccine is whether it's going to be protective or not. The Mirr's study was absolutely critical, says Tom Evans, chief scientific officer of Vaxateech. We could say, okay, we can start tomorrow. We don't have to make ten different varieties of this. We knew it could be manufactured, we knew

it was immunogenic in humans. When she first heard about the cases of pneumonia in China over the new year, Gilbert was unsure how quickly it would spread. We didn't know what it was. Early on, she says. I was talking to colleagues, thinking, yeah, as soon as the sequence comes out, we'll make something. We'll test it in mice, we'll show what we can do. The moment the Chinese scientists published the genetic sequence of the novel coronavirus on

January tenth, Gilbert got to work. Oxford had an advantage unusual for an academic institution, its own vaccine manufacturing facility, at which it was able to quickly manufacture the shot for the first phase of human trials. Gilbert arranged for the next larger batch to come from Italian farmer company Advent, and persuaded the university to underwrite the contract until she

could secure further funding. On February, her team began injecting mice with a vaccine to accelerate a process that normally takes months. She was performing several steps at once, testing in animals, applying to regulators for human trials, and talking to manufacturers. Her level of knowledge of the detail is extraordinary, says Andrew McLean, who worked with her for years as

an investor and board member at VACKS attack. It's very unusual for a scientist to know the practical parts of getting a drug made and be able to talk to manufacturers on a toe to toe basis. But in early March Gilbert was still scrounging for money. She got a small grant from the Coalition for Epidemic Preparedness Innovations or c e p I, a foundation set up in twenty seventeen with funding from the Bill and Melinda Gates Foundation, the governments of Norway in India, and the Welcome Trust,

a research charity based in London. It was enough to keep them going Around this time, there was a debate within the Gender Institute about whether to go straight into human trials or wait until they got results from a study of their vaccine in nine REESUS monkeys at the Rocky Mountain Laboratories in Montana, part of the n I A I D. They knew that in tests for a vaccine against the first Stars virus, which caused an epidemic in Asia in two thousand two and three, some vaccinated

animals became more severely ill after they were challenged with the virus than unvaccinated ones did. The phenomenon is known as antibody dependent enhancement or a d E. Scientists around the world were worried that might happen again with the Stars Cove two vaccine, and the Oxford team wanted to test it in monkeys to rule it out, but time was of the essence. People were dying from COVID nineteen and waiting for the monkey results would mean losing crucial weeks.

We were doing that monkey experiment for safety and to convince the pessimists that the vaccine was going to be safe after infection. Hill says, the big question was when you have a vaccine available, and you have people lined up ready to go. Do you wait for the monkey results to vaccinate them? They decided to play it safe and wait, while pressing ahead with planning the trials, setting

up manufacturing, and looking for more money. On March twenty third, the same day UK Prime Minister Boris Johnson ordered the country into lockdown, the government announced a two point two million pound grant to Gilbert's team to support testing and manufacturing. During the search for money, Bill Gates pushed Gilbert and Hill to partner with a big pharmaceutical company, and as

a C E p I founder, he had leverage. We went to Oxford and said, you are doing brilliant work, Gates recalled in a call with reporters in early June. You really need to team up, and we told them a list of people to go and talk to. The Oxford team was initially reluctant, Hill says, because they'd run plenty of trials on their own. What we struggle against all the time is the perception from fonders that we

can't do this, he says. They held talks with several potential partners, whom he declined to name, asking them two questions, how much can you manufacture and by when? They didn't answer either of those questions, no matter how many times we asked, Hill recalls astra Zenica was different. In early April, Minne Pangalos, the company's head of research and development for biopharmaceuticals, had been hearing positive things about Oxford's work. Although astra

Zenica isn't a big player in back scenes. It produces a nasal flu spray vaccine, but nothing else. He thought it was worth calling John Bell, an immunologist and professor who directs the university's medical research strategy, to find out more. It seemed like they needed a partner, Pangalos recalls. I called John up and said, are you interested in working with us on this because we think we can help.

Pangalos negotiated the partnership agreement with Bell and the rest of the Oxford team in about ten days through a flurry of zoom calls, with Gilbert walking everyone through the data. Astra Zeneca agreed to be responsible for worldwide distribution and manufacturing. Big money followed the announcement of the deal at the end of April. As Pascal Sorrio, astra Zeneca's chief executive officer pledged to make the vaccine available at only a

few dollars per dose. The British government gave sixty five million pounds to accelerate the work and order thirty million doses for the UK by September, as part of a deal to make one million in total, with some reserve for de heloping countries. Days later, astra Zeneca announced a one point to billion dollar deal with the U s Biomedical Advanced Research and Development Authority BARDA to develop and produce three hundred million doses, one of the largest deals

the agency has announced. Astra Zeneca will work with the National Institutes of Health to test it in thirty thousand people in the US, scheduled to start in August. The company later struck a licensing deal with the Serum Institute of India to produce a billion doses for developing and middle income countries. Because of expected political pressure, any country with a role in the production of a vaccine might

act to secure doses for its own people. Astra Zeneca is setting up independent supply chains within countries to prevent delays at national borders. As the astro Zenica deal was being finalized in mid April, the results of the monkey study came through from Montana. It wasn't promising, it was fantastic. Hill says. Not only were the monkeys fine, it as

a bonus we saw some protection. They had vaccinated six monkeys and then twenty eight days later, exposed them to a massive dose of stars COVID two via multiple roots, eyes, mouth, nose, and trachea to expose the lungs. It was much more than a person might encounter on public transportation or even in a COVID Ward after exposure, the animals showed no signs of pneumonia in their lungs by all indications, They felt fine. Nasal swabs, however, showed they still had the virus,

meaning they might be able to infect others. The study's aim was to determine safety, not efficacy, so the gender team was encouraged to see it provided some protection in the face of an overwhelming dose of the virus. The day after the preliminary results came in, a team headed by Andrew Pollard, a colleague of Gilbert's, running the clinical trials, started injecting people. When the full results of the monkey trials were published in mid May, critics pounced seeing the

results as weak. William Hazeltine, a former professor at Harvard Medical School who spent years researching HIV, wrote a piece in Forbes arguing that the Oxford vaccine looked like it would be only partially protective because it didn't generate high levels of neutralizing antibodies, which defends cells against infection. What happens when you have a vaccine with people running around

with virus spewing out of their nose. Anyone who is not vaccinated or not vaccinated well is going to get infected, Hazeltine told me on a zoom call. My guess is the Oxford vaccine isn't going to be powerful enough for older people, so they will have to boost it up, and boosting it up can have side effects. On July fourteenth, the U. S. Government released results from the safety trial

of another vaccine candidate from Maderna. The company's stock rose sharply on news that the vaccine produced neutralizing antibodies in all patients. It also produced side effects in some Maderna's vaccine, produced using a technique called Messenger RNA, will go into late stage trials by the end of July. Team Oxford Astra Zeneca argues it's not realistic to expect clear nasal swabs from monkeys after they got a whopping dose straight up their noses. It doesn't need to cure you of

stars cove too. Astra Zeneca's Pungalow says, I don't know if we will completely knock out shedding or people being infectious, whether we're going to cure people completely, or whether we will just dampen down the illness. We want a vaccine to stop people from going to hospital and dying. If you can do that, I think people will be pretty happy. Neutralizing antibodies is one of the things you'll look at, but the T cell response is going to be important.

Hill says the same thing. Has Alten's focus on neutralizing antibodies is misplaced scientific debates aside. I was starting to sense a Harvard Oxford American British rivalry playing out. It's simpler to measure antibodies, it's less expensive. People do it all the time, But often the antibodies are a surrogate

for the T cell number. Hill says, nobody knows in SARS, in mers and in COVID nineteen the relative importance of those two A flurry of recent research has shown that T cells may play an important role in responses to SARS cove two, but the only way to know the most effective levels or tighters of antibodies and T cells is to test the vaccine in people where the virus is circulating. No one knows how strong the immune response needs to be to achieve protection in people of any age.

Gilbert says, if we get a strong T cell response, we don't need such a high neutralizing antibody tighter to achieve protection. The two arms of the immune response work together to give better protection. The Gender Institute team is taking blood samples of people in the trials that begin in late April and May in the UK to measure antibodies and T cell responses several weeks after vaccination, but blood results can't prove it will prevent disease. It's a

numbers game. They're looking for very few cases of COVID nineteen in people who have received the vaccine, and a significantly higher number in a control group of people who haven't. The better the vaccine is, the quicker you get a result, and the smaller number you need. Hill says, if they reach say twenty cases in the control group and eighteen among the vaccinated cohort. That's not a great vaccine, and they would need a lot of cases to show a difference.

But if you have twenty in the control group and two among the vaccinated, your home and dry, he says. Of course, a quicker way of figuring out if it works would be to stage human challenge trials like those done with the monkeys. So far, no COVID nineteen vaccine developer has used to challenge trials because of ethical concerns and the lack of an effective treatment for the disease.

That hasn't stopped more than thirty thousand people from more than forty countries from registering to take part in a potential challenge trial through an organization called One Day Sooner. When I asked Gilbert in April what was worrying her the most, she said it was going to be difficult to prove the vaccine works as the virus waxes and

wanes around the world. In order to determine vaccine efficacy for any novel coronavirus vaccine, the trial has to be set up in the right place at the right time, and that's very hard to predict she said, it's why we're planning to do multiple trials in multiple countries. In early June, as UK cases began to drop, astra Zenica set up trials of the vaccine in Brazil and South Africa,

where the virus is surging. Producing millions, if not billions, of doses of the vaccine may be the biggest challenge in the history of the pharmaceutical industry. Astra Zennica is signing production agreements with companies worldwide, including Oxford Biomedica, a small gene and cell therapy company at ten minute drive from the Gender Institute. Oxford Biomedica has agreed to produce several million doses, with the potential to scale up into

the tens of millions if it works. James Miskin, the company's chief technical officer, describes a multi step production and process that sounds to my lay person's ears like a cross between making a sour dough starter and boiling down sap to make maple syrup. It begins with nurturing a few milliliters of human embryonic kidney cells kept in a frozen vial that needs to be gradually defrosted as the cells are fed a sugar solution they multiply in a

controlled atmosphere of oxygen and carbon dioxide. Over the course of a week. The mixture is moved into larger and larger vessels and eventually into a two stainless steel bioreactor. The master seedstock of the vaccine, which contains the adenavirus with the spike protein, is added to the soupy mixture,

which is stirred, purified, concentrated and filtered down. Scaling the process up to get to millions of doses is full of unknowns, says Matthew du Chars, CEO of the UK government funded Vaccines Manufacturing and Innovation Center, which is helping coordinate British manufacturers. I asked him about the soured analogy.

It's like trying to go from making a loaf of sour dough in your kitchen to making a hundred thousand sour dough pizzas he says, scale up of any process is never as simple as you think it will be, especially with biological material. At the end of May, Gilbert's team pressed ahead with more advanced trials on more than ten thousand people in the UK after getting the green light from an independent scientific panel that reviewed its progress

so far. To be ready to go, the Oxford group had spent several months working with Advent, the Italian manufacturer, to produce the vaccine for the large scale trials. Under the eye of Stephania Di Marco, a biochemist and advanced scientific director. Advance staff worked into the evenings and over weekends to produce thirteen thousand doses of the vaccine at a time when Italy was the epicenter of the COVID

nineteen pandemic. With the seed stock, they made one liters of unpurified product and reduced it down to about three leaders of vaccine. On May fourth, they'd finally reached the stage where they could start filling glass vials with the vaccine. DeMarco and about fifteen people from her team of twenty five gathered that evening as the filling began, with some tears and hugging. We were excited, she says, this is

precious material. Two weeks later, after extensive checks and documentation, the first shipment of the vaccine arrived in Oxford in temperature controlled boxes. At the end of May, advanced batch of vaccines started going into people over the age of fifty five to find out if there's a variation in immune responses to the shot in people of different ages.

How the vaccine performs in this much larger and more diverse group, particularly older people, could well determine whether the Oxford vaccine will help end the pandemic or whether the world must continue to wait. With Vernon Silver and James Patton, thanks for listening to this week's cover story. Check out this week's magazine for more stories, including one on America's richest man opening up about COVID risk and luck the issue.

Keep in mind it's on news stands right now. You can also find it online at Bloomberg dot com and always on the Bloomberg terminal. I'm Carol Masser and I'm Jason Kelly, and also be sure to check us out every day on the radio, Bloomberg Business Week runs two pm to six pm Wall Street Time. Also download our podcasts, subscribe to her everything we're doing This is Bloomberg