For five days, the FedEx plane stood on the tarmac in Shanghai.
American scientists from Novavax, a biotech company in suburban Maryland, waited with growing impatience. The plane contained a copy of a newly discovered key coronavirus gene. Novavax needed the gene to try to develop a vaccine.
Scientists had been in similar situations before. Whenever a new disease arose – SARS, MERS, Ebola – they produced candidate vaccines to see if they could tame it. They thought of their research as an experiment.
But the longer the plane got stuck, the more they wondered if this time it couldn̵
As of January 30, the fourth day, the virus still had no name, but was already present in dozens of countries, making more than 8,200 sick and killing 171 people, most in the city of Wuhan, China. Every day the Novavax researchers waited meant that another day they couldn’t try to help.
Novavax R&D president, Dr. Gregory Glenn, picked up the phone that day, a Thursday. He called GenScript, the company that had copied the gene in China, and persuaded the company to do it again, this time in its laboratory in Piscataway, New Jersey.
By late Sunday night, the gene was ready. GenScript’s vice president of sales for North America hopped into his car and drove it south for four hours, arriving at 2am on Monday, February 3. Glenn was there to meet him.
Novavax had been through a difficult time. Four months earlier, he had been “left for dead,” Glenn said after his vaccine candidate for a childhood virus called RSV failed a crucial test. The staff had been reduced from 800 to 50.
Some of the company’s senior executives wanted to continue pursuing that vaccine and complete the only research study they still had money to complete. But Glenn argued that it would be a huge mistake to miss the chance to fight a new virus that was getting scarier by the hour.
Other companies were beginning to see vaccine development as a once-in-a-century crisis that they could help win.
For nine months, researchers around the world have been racing to develop a vaccine against SARS-CoV-2, the virus that causes COVID-19, which on its deadliest day in the United States killed nearly as many people as died. Sept. 11. , 19 years ago today.
Dozens of groups work days, nights and weekends, fueled by coffee, competitiveness and the desire to protect the world. And probably make money along the way.
Six of these teams have received pledges totaling more than $ 10 billion from the United States government, with probably one or two more billion-dollar contracts. That expense – one of the largest ever on public health – will fund the development of six to eight vaccines and at least 100 million doses of each.
If everyone is successful, there will be plenty of vaccines for everyone in the US who wants a shot.
If they all fail, it’s back to square one, with staggering amounts of worthless product poured down the drain, and nothing to offer millions of anxious and weary Americans.
Interviews with more than eight leading companies involved in US efforts reveal a complex process of countless hours, fingers crossed and restless nights but, so far, no total failure.
The teams are in different stages of development, but each has undertaken key studies to prove safety and efficacy.
The results of large trials, which will begin to trickle next month, will reveal who will cross the line in the race for a COVID-19 vaccine. And who – if any – will fall flat in the attempt.
‘Dizzying complex’: What we know about how a vaccine will be distributed
Vaccine test: AstraZeneca’s trial is on hiatus after an illness. What does this mean?
Three days into the New Year, Kate Broderick was in the kitchen making a cup of Scottish Blend tea and browsing the BBC website on her phone.
“There was this article in the health section about an unknown pneumonia in China. I thought, ‘This is interesting. I should keep an eye on him.’
Scottish molecular geneticist, Broderick was one year in a new position as senior vice president of research and development at Inovio Pharmaceuticals, where he had worked for 14 years.
She and her team at Inovio, which creates synthetic DNA-based products to treat cancer and infectious diseases, have begun digging into the coronavirus literature.
A week later, when researchers from China and Australia published the genome of the virus, his team was ready. “We had trained all of our lives for it,” he said.
Within hours, just after midnight on January 11, Inovio researchers in Philadelphia uploaded the genetic sequence to a computer. They hoped their algorithm could focus on some protein that could be targeted with a vaccine.
The three hours Broderick spent at the company’s San Diego research center waiting for news from Philadelphia were among the longest of his professional life. “It was almost thrilling,” he said. “There were a lot of messages going back and forth: ‘Has this already been done?'”
When the computer spat out the protein that their algorithm had chosen as most likely, they started right away, working until that Friday night. By the end of Saturday they had designed a vaccine candidate. Broderick has rarely had a day off since.
“For a while, I slept on average about two hours a night,” said Broderick, who had to juggle researchers from Philadelphia, Australia, China and Europe. “Just the time zones and maintaining partnerships was complicated.”
Making it work meant taking naps when possible and eating when the weather allowed. It meant endless Zoom meetings, up to 10 per day, sometimes wearing work clothes on top and “jammies” underneath.
“Just when you think you can sit down and have a glass of wine, then Australia wakes up or China wakes up and it’s, ‘Ding, ding, ding,'” Broderick said. “Sometimes you have to be hard on yourself to put on” Do Not Disturb “”.
Stéphane Bancel was entertaining with the richest and most powerful people in the world, hoping to get a head start for his 10-year-old biotech company, Moderna.
During the breaks in the four days At the World Economic Forum conference, when there was no one to shake hands with, the native Frenchman sat in the corner with Dr. Jeremy Farrar, director of the Wellcome Trust, a scientific charity, and Dr. Richard Hatchett, CEO of the Coalition for Epidemic Preparedness Innovations (CEPI), a public-private partnership that supports vaccine development.
The three were drawing bar graphs on a napkin.
Hatchett and Farrar, world experts in vaccine research, were getting the latest infection data from China. An unusual epidemic of pneumonia was tearing apart a city there. Their raw bars kept getting longer and longer.
Bancel had to pull out his iPad to search for the unknown city: Wuhan. Then he saw its size and its many daily air routes. And he knew.
Despite Chinese assurances that the disease was under control, Hatchett, Farrar and Bancel realized that this was the epidemic they had predicted – and feared – for years.
Bancel called his staff in Cambridge, Massachusetts, and told them to step up the work they had just started consider developing a candidate vaccine against COVID-19.
“We have to think big. This is not an outbreak. It could be a pandemic a la the Spanish flu of 1918, “Bancel told them.” They thought I was crazy. ”
Roger Connor had spent a lot of time on the phone with his boss, GlaxoSmithKline’s London CEO, Emma Walmsley. They usually talked a couple of times a week. It had been every day lately.
Connor had recently spoken with Hatchett, the head of CEPI, who had told him that the Chinese situation could be a “worldwide epidemic”.
This got Connor’s attention. The Northern Irish native was already leading a crisis team for GSK, caring for employees in China affected by the disease.
“This was a real moment that made us think we would need to look at other scenarios,” Connor said. which oversees GSK’s 17,000-person global vaccines division from its base in Brussels.
During his call with Walmsley on Jan.24, Connor began brainstorming what solutions GSK could offer to a global community that will soon be overwhelmed by this new virus.
“We are the biggest vaccine player in the world. We have been involved in pandemics before. We knew we had to be a part of the solution,” Connor said.
The couple looked into GSK’s potential vaccine technologies. But Connor and Walmsley concluded that they could have better hedged their bets by pursuing an adjuvant rather than a vaccine.
An adjuvant adds punch. Allows you to use vaccines at lower doses, while preserving a valuable resource. It makes vaccines work better in people with weaker immune systems, such as those aged 65 and over, who account for 80% of COVID-related deaths in the United States.
And an adjuvant can be used with a variety of vaccines, so if one fails – as about two-thirds of candidate vaccines eventually do – a GSK product could still find a market. One that required the sale of billions of doses.
President Donald Trump led the West Wing meeting from the center of a long conference table, Vice President Mike Pence on his right and Secretary of Health and Human Services Alex Azar on his left.
Interviewed with other government officials, pharmaceutical executives like Walmsley and Bancel talked about what they were doing to fight the pandemic.
Trump seemed worried about one thing: how soon can you prepare a vaccine? Faster than the others?
Sanofi’s John Shiver said his company’s candidate vaccine could be delivered to the first person in perhaps about a year. “Hard to predict, Mr. President, knowing that a vaccine has to be both safe and effective because it is given to healthy people,” he said.
Stanley Erck, CEO of Novavax, has pledged to start much earlier, with a small Phase 1 trial by May or June. Inovio has promised to launch one in April.
Moderna’s Bancel said he was ready to start each day; he was just waiting for government approval.
“You will not have a vaccine. You will have a vaccine to go to test, “Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, cautioned after Bancel spoke.
Injecting a few shoulders as part of a trial was very different from being able to inject hundreds of millions of Americans with a safe and effective vaccine.
Trump focused on shorter lead times when summarizing what he had heard “This is amazing news. And I think the speed is much greater than many people would have thought,” said Trump, who used a version of the word. fast ”10 times during the one-hour meeting.
As the meeting drew to a close, a reporter asked: “Is it realistic to think, really, that a vaccine could be ready in three or four months?”
“Well, you have the largest companies in the world sitting around the table,” Trump replied. “I mean, Johnson & Johnson and Pfizer and all the companies… you have all these big companies and that’s what they’re saying. So I think -“
Fauci intervened. Someone had to get the president to explain the steps involved in bringing a vaccine to market for the general public.
“Would you make sure you get the president the information that a vaccine you make and start testing in a year’s time isn’t a vaccine that can be distributed?” Fauci begged. “It will be, at the earliest, a year to a year and a half, no matter how fast you go.”
The patient’s shoulder was exposed. A syringe rapidly injected the candidate vaccine, mRNA-1273, developed by Moderna and the federal government.
The vaccine, like others, targets the spike protein on the outside of the coronavirus. But the technology is new and employs a genetic messenger that tells a person’s cells to create the virus’s signature protein, causing their body to recognize and fight the invader.
The approach is innovative and fast – and has never produced an approved product.
The shot marked the start of the first human trials against COVID-19, the start of Phase 1. It was only 63 days since the publication of the virus’s genetic sequence.
“There is no doubt that this is the indoor world record,” Fauci later said. “I’ve never seen anything go this fast.”
Dr. Philip Dormitzer had already targeted new viruses: the 2009 swine flu and the 2013 H7N9 flu. But he had never had the red carpet rolled out like this.
Whatever he needed to prosecute SARS-CoV-2, all he had to do was ask.
“Our CEO Albert Bourla said very early on, do whatever it takes to be successful. If you need a resource, ask for it and you’ll get it,” said Dormitzer, chief scientific officer for viral vaccine R&D with pharmaceutical giant Pfizer, Inc. .
If he needed to transport samples, suddenly the corporate jet and helicopters were available.
“I always had to justify everything I was doing in the budget,” said Dormitzer, who made the leap into pharmaceutical companies after a dozen years as an infectious disease pediatrician, mainly at Harvard University. “This is a level of support I’ve never experienced before. I shouldn’t get used to it.”
Even though she knew people who contracted the flu in 2009 and 2013, that was nothing like what was happening as winter turned into spring in the New York City region where she lives and works.
He was amazed, he said, at the dedication of the 350 employees who showed up each day at the Pfizer facility in Pearl River, wearing masks, propping up open doors so they wouldn’t touch the handles, and working as fast as possible to prepare. a vaccine for human testing.
Like other companies, Pfizer executives were initially unsure whether they should pursue a COVID-19 vaccine.
The vaccine industry had learned a lesson from previous pandemics such as SARS, MERS, Ebola and influenza – many are exhausted on their own or with public health measures. It’s great for humanity, but not so good for a company that needs to justify its financial investment in a candidate vaccine.
As SARS-CoV-2 spread to the United States, Pfizer executives were faced with a fundamental question: Could the company financially justify developing a vaccine against it?
The answer came from the daily news. The bar charts that Bancel had started drawing on napkins just six weeks earlier they were going up.
Unlike SARS or MERS, many people infected with SARS-CoV-2 were not sick enough to retire quickly to bed. They were more likely to transmit the disease.
On April 9 Pfizer signed an agreement to collaborate with the German company BioNTech. Pfizer began testing four of BioNTech’s candidate vaccines, all variants of the same mRNA technology used by Moderna. The study included 13 different groups, with 15 volunteers each. Some received a placebo, others several doses of the potential vaccines.
“We were lucky,” Dormitzer said. The two most feasible large-scale experimental vaccines also showed good results.
Both seemed safe and triggered a better immune response than a natural infection, at least in the measures they tested. But one looked even better in older people.
Indresh Srivastava has spent his professional life making vaccines. He co-wrote the book that people use to learn about vaccine development and manufacturing.
If I had asked him in February how long it would take to prepare a vaccine candidate for clinical trials, he would have said at least a couple of years.
Now he was trying to prove he was wrong.
Srivastava, originally from India, runs the Sanofi Protein Science site in Meriden, Connecticut. He helped develop the groundbreaking flu vaccine that triggered Sanofi’s purchase of Protein Sciences in 2017.
Over 80% of the flu vaccine produced in the United States each year is grown in chicken eggs, hundreds of millions. The process takes about six months, which means that the strains used in the vaccine must be chosen more than six months before the flu season, although the flu virus constantly mutates.
They mutate so much that the strains placed in eggs are sometimes not the ones that come out, which could be one reason why the flu shot isn’t always highly effective.
Srivastava and her team got around the problem by growing the flu vaccine with the help of an insect virus instead of eggs, substantially reducing development time.
Now, Sanofi wanted him to grow the SARS-CoV-2 spike protein in the same virus as the bug.
His team began rotating shifts, seven days a week, wearing personal protective clothing and keeping as physically distant as possible in the lab.
The technicians performed each of the normal steps as quickly as possible, working in parallel instead of the usual sequence. They chose materials that they could easily purchase on a large scale.
They added the spike protein DNA to the bug virus and grew it in a giant bioreactor, purifying the results.
The process took nine days to complete from start to finish. Any mistake would set them back at least a week.
Srivastava said she spent several difficult nights wondering what she would do if it didn’t work out. “I couldn’t find an answer to my question,” he said.
But with a small team focused on each major step, only two batches were needed to prove their process worked. They produced enough material for a Phase 1 study and outlined plans for the much larger Phase 3 they hoped would follow.
“It was a technology we understood well,” said Shiver, global head of vaccine research and development at Sanofi.
On April 11, BARDA gave Sanofi the green light to proceed with Phase 1; on the 14th, Sanofi and GSK signed an agreement to combine Sanofi’s vaccine with GSK’s adjuvant.
Although so many people felt powerless against the pandemic, Shiver said Sanofi employees working on the vaccine felt empowered.
“We are in a unique position to really do something,” Shiver said.
Nicholas Kartsonis, like many others in vaccine development, worked seven days a week for months.
Kartsonis and his team at Merck looked at thousands of compounds to see if they could produce effective vaccines. They looked at 250 possible partnerships with other companies to develop a vaccine.
While other companies began testing their candidate vaccines on people and garnering billion-dollar promises from the federal government, Merck was still at the drawing board.
Eventually, by the end of April, they had narrowed their options to two vaccines. One, dubbed v590, was based on a similar vaccine that Merck had licensed to fight Ebola.
That vaccine, approved last year, used a virus common in cows to transport the spike protein into human cells. “We understand the manufacturing processes,” said Kartsonis, who leads clinical research on infectious diseases from the Merck site in West Point, Pennsylvania, a 45-minute drive north of Philadelphia.
If Merck could produce an effective COVID-19 vaccine like the one against Ebola, he said, it would overshadow its competitors. With the Ebola vaccine, 95% of those vaccinated were protected for at least three years.
Also, since the virus that releases the vaccine makes copies of itself inside the human body, one dose should be enough to protect itself from COVID-19. All other vaccines backed by US funding will require two shots each.
Merck’s second candidate vaccine, v591, also replicates in the body, so one dose should be protective. It is based on a collaboration with the Austrian Themis Bioscience.
“We would really like to have a single-dose vaccine,” Kartsonis said, noting that both of its candidates are based on “tried and tested platforms”, while its competitors use more innovative technology. “We really wanted to do something that complemented what others were doing.”
All 7.7 billion people on the planet cannot be protected with just one vaccine. Using vaccines that work differently increases the chances of protecting everyone from babies to pregnant women to the elderly who do so badly when they catch COVID-19.
Merck has not yet obtained a commitment from the federal government to finance production, but the the week before Memorial Day, the threads Kartsonis had been working on for months have finally begun to come together. After the holiday weekend, Merck entered into a deal to buy Themis and gain control over the v591. He signed a collaboration agreement to develop v590 and another to develop an antiviral.
Merck wouldn’t be the first to produce a vaccine, but it would have two strong contenders.
“If Moderna and Pfizer, who are in the lead now, if their vaccines work, I’ll be the first person to have a happy dance in my office,” Kartsonis said, although it would be behind closed doors, he added, because his dancing. it is not suitable for public viewing.
They don’t care which company gets a vaccine first. Kartsonis just hopes that the pharmaceutical industry, which doesn’t have the best public reputation, can prove it can make a positive difference in the world.
“I want my kids to go back to school like everyone else does, regardless of whether it’s Merck or not Merck.”
Just before 7am, TV host Dawn Baker rolled up her sleeve, baring her upper arm. The needle that hit her contained a dose of the candidate vaccine developed by Moderna and Fauci’s agency.
It had to be kept very cold, but not minus 94 degrees Fahrenheit, as it had done earlier in research. This marked a triumph for the scientists who had struggled to make their product more stable so that it would remain effective when stored in a regular freezer rather than at dry ice temperature.
Baker, an anchor at the CNN affiliate WTOC in Savannah, was the first of 30,000 people in the phase 3 study, half of whom would receive the active vaccine and half a placebo.
She told a CNN interviewer that she hoped to become a role model – as a participant in the trial and as a black woman in that trial.
“I’ve heard a lot of my friends and even relatives saying that, you know, ‘I’m not going to be the first person to get this vaccine. I don’t want to be the guinea pig. I’ll just wait and see what happens first,'” Baker told viewers. “I hope maybe just seeing my face will help them change their views.”
A few hours later, Fauci and Dr. Francis Collins, head of the National Institutes of Health, held a press conference to promote the start of the Phase 3 process.
Collins described the research as “a great American opportunity for people to come on board as our partners, to try and take part in what has been a historic effort to end the worst pandemic our world has seen in over 100. years”.
Later that afternoon, Pfizer silently announced that she too had started a Phase 3 trial for 30,000 people.
Parlando alla televisione di stato, il presidente russo Vladimir Putin ha annunciato che un vaccino prodotto a Mosca era stato approvato per uso generale. “Ha superato tutti i test necessari”, ha detto.
Ha dichiarato che la Russia aveva vinto la corsa per un vaccino.
Lo scatto si chiamava Sputnik-V, in ricordo del satellite Sputnik dell’Unione Sovietica, che sorprese il mondo nel 1957 quando divenne il primo oggetto artificiale a orbitare con successo intorno alla terra.
Gli scienziati fuori dalla Russia erano scettici. Semplicemente non c’era stato abbastanza tempo per produrre un vaccino e testarlo su migliaia di persone.
“Non sono sicuro di cosa stia facendo la Russia, ma di certo non prenderei un vaccino che non sia stato testato in Fase III”, ha detto Florian Krammer, professore di vaccinologia presso il Dipartimento di Microbiologia presso la Icahn School of Medicine del Monte Sinai. Twitter. “Nessuno sa se è sicuro o se funziona.”
Secondo un’altra misura, la Cina aveva già vinto.
A giugno, il governo cinese ha annunciato di aver avviato la vaccinazione diffusa dei membri del servizio militare – essenzialmente conducendo un processo sui suoi soldati – anche se poco è confermato e non è chiaro se qualcuno studierà le loro reazioni.
Ogni venerdì pomeriggio, il team della dottoressa Macaya Douoguih a Janssen Vaccines tiene una videoconferenza per aggiornarsi a vicenda sui propri progressi.
“È stata davvero una buona notizia per molte settimane consecutive”, ha detto Douoguih, teletrasportata dal suo ufficio a L’Aia. “Finora non abbiamo visto sorprese – no, ‘Oh Dio, questa è una battuta d’arresto!'”
Douoguih, che ha frequentato la facoltà di medicina presso l’Università di Washington, dirige lo sviluppo clinico e gli affari medici presso le società farmaceutiche Janssen di Johnson & Johnson, i cui uffici hanno sede a Leida, a circa 12 miglia da casa sua.
Il lavoro è stato ininterrotto da marzo, ha detto. Creare un vaccino contro il coronavirus è sia uno sprint che una maratona.
“È una di quelle cose in cui a un certo punto ti rendi conto, ‘Wow. Sono davvero stanco, “e inizi a piangere spontaneamente”, ha detto Douoguih.
Poi torna a lavorare.
Sotto la sua direzione, sono in corso le prove di fase 1 e 2 e prevede che le prove di fase 3 inizieranno entro la fine del mese.
Sanofi e GSK hanno recentemente lanciato una prova di fase 1-2 combinata di 440 persone negli Stati Uniti. La v591 di Merck è in fase 1 e la v590 sarà presto disponibile. La società, che finora ha ricevuto solo 38 milioni di dollari in denaro federale, spera che sussidi più grandi non saranno molto indietro.
Giorno dopo giorno, gli stessi produttori di vaccini non sanno come sta andando il loro candidato. I dati vengono “accecati” finché non raggiungono determinati traguardi.
Dopo aver corso a ritmo vertiginoso per mesi, Douoguih, Srivastava, Kartsonis e altri sviluppatori di vaccini devono sedersi sulle mani e aspettare i risultati della sperimentazione.
Novavax President Stanley Erck, whose company is now back up to 400 employees from a low of 50, said he lives for those moments – the good ones, anyway – when the spreadsheets reveal a study’s results.
He won’t soon forget the Sunday morning he and his chairman and head of R&D sat around the kitchen table at his Bethesda, Maryland, condo, getting the first glimpse of their Phase 1 results.
“There was some fist-bumping,” he admitted.
And strong feelings of relief.
A vaccine trial can go bad, even if the vaccine is good. The vaccine shipment might have sat on the tarmac in the heat, like the gene had, while its fragile proteins disintegrated. “There are 100 things that can go wrong, that doesn’t necessarily mean your vaccine doesn’t work,” Erck said.
Six months to the day after the declaration of the pandemic, AstraZeneca now sits on that precipice.
All the U.S.-backed vaccine makers have enjoyed months of nearly continuous progress and good news.
But Tuesday, AstraZeneca, one of three companies already in Phase 3 trials, halted its COVID-19 trials worldwide. One participant in Britain apparently developed a neurological condition.
All the lab research, mouse and monkey studies, months without weekends and millions spent could be derailed by a side effect in a single patient.
For now, it’s just a routine pause. The illness might not have been caused by the vaccine at all. It’s not a surprise to see a health issue in a trial that includes lots of older adults and those with medical problems.
The trial could pick up in a week or two if the vaccine can be easily cleared.
“We will know at some point whether the vaccine works and if it’s safe,” AstraZeneca CEO Pascal Soriot said Thursday. “We just have to be patient.”
The company, which licensed its candidate vaccine AZD1222 from Oxford University, has already started making a planned 3 billion doses on four continents. It has the potential to make a significant dent in the global need for a vaccine.
Soriot said AstraZeneca, like many of the companies, will sell its vaccine without profit during the pandemic. That should prove particularly helpful for poor countries.
“We need to offer access to everybody as quickly as possible,” Soriot told his mostly British audience, speaking in the thick accent that confirms his French origins.
AstraZeneca also is under contract to produce 300 million doses for Americans – three times as many as the other companies because government officials had seen it as the most promising of the contenders.
This one person’s illness, if tied to the vaccine, could derail AZD1222. Or the candidate vaccine and others might not prove effective enough to justify approval.
Either way, the race for a COVID-19 vaccine continues. The world watches. And waits at the finish line.
Mike Stucka contributed to this report.
Contact Karen Weintraub at email@example.com and Elizabeth Weise at firstname.lastname@example.org
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