Timeline of companies’ progress on phases

For five days, the FedEx plane sat on the tarmac in Shanghai.

American scientists at Novavax, a biotech company in suburban Maryland, waited with increasing impatience. The plane held a copy of a key gene from the newly discovered coronavirus. Novavax needed the gene to try to develop a vaccine.

The scientists had been in similar situations before. Every time a new disease came along – SARS, MERS, Ebola – they made candidate vaccines to see whether they could tame it. They thought of their research as an experiment.

But the longer the plane remained stuck, the more they wondered if this time might not be a drill.

By Jan. 30, the fourth day, the virus still lacked a name, but it already was in dozens of countries, sickening more than 8,200 and killing 171, most in Wuhan City, China. Every day the Novavax researchers waited meant another day they couldn’t try to help.

Novavax president of R&D 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 firm to make it again, this time at its lab 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 four hours south, arriving at 2 a.m., Monday, Feb. 3. Glenn was there to meet him.

Novavax had been through a tough time. Four months earlier, it had been “given up for dead,” Glenn said, after its candidate vaccine for a childhood virus called RSV failed a crucial trial. The staff had been cut from 800 to 50.

Some of the company’s senior leadership wanted to stick to pursuing that vaccine and follow through on the one research trial they still had money to complete. But Glenn argued it would be a huge mistake to pass up 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 they could help conquer. 

For nine months now, 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 U.S. killed nearly as many people as died on 9/11, 19 years ago today. 

Dozens of groups are working days, nights and weekends, fueled by coffee, competitiveness and the desire to protect the world. And likely make money along the way. 

Six of those teams have received promises totaling more than $10 billion from the U.S. government, with one or two more billion-dollar contracts likely to come. That spending – one of the largest ever for public health – will fund development of six to eight vaccines and at least 100 million doses of each. 

If they all succeed, there will be plenty of vaccine for everyone in the U.S. 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 the U.S. effort reveal a complex process of countless hours, crossed fingers and restless nights but, so far, no utter failures. 

The teams are at different stages of development, but each has begun key studies to prove safety and effectiveness.

The results of large trials, which will begin trickling in as soon as next month, will reveal who will cross the finish line in the race to a COVID-19 vaccine. And who – if anyone – will fall flat trying.

‘Mind-bogglingly complex’: What we know about how a vaccine will be distributed 

Vaccine trial: AstraZeneca’s trial is on pause after an illness. What does this mean?

Three days into the new year, Kate Broderick was standing in her kitchen making a cup of Scottish Blend tea and browsing through the BBC’s website on her phone.

“There was this article in the health section about an unknown pneumonia in China. I thought, ‘That’s interesting. I should keep my eye on it.’”

A molecular geneticist from Scotland, Broderick was a year into a new position as senior vice president for research and development at Inovio Pharmaceuticals, where she’d worked for 14 years.

She and her team at Inovio, which creates synthetic DNA products to treat cancer and infectious illnesses, began digging into the literature on coronaviruses.

A week later, when researchers from China and Australia published the virus’ genome, her team was ready. “We’d trained all our lives for this,” she said.

In a matter of hours, just after midnight on Jan. 11, Inovio researchers in Philadelphia uploaded the genetic sequence to a computer. They were hoping their algorithm could home in on a bit of protein that could be targeted with a vaccine.

The three hours Broderick spent in the company’s San Diego research center waiting for news from Philadelphia were among the longest of her professional life. “It was almost emotional,” she said. “There were lots of texts going back and forth: ‘Is it done yet?’”

When the computer spit out the protein their algorithm had chosen as the most likely, they started in right away, working through 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 was averaging about two hours sleep a night,” said Broderick, who had to juggle communications between researchers in Philadelphia, Australia, China and Europe. “Just the time zones and maintaining the collaborations was complicated.”

Making it work meant catching naps when possible and eating when time allowed. It meant endless Zoom meetings, up to 10 a day, sometimes wearing work clothes on top and “jammies” on the bottom. 

“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 strict with yourself to put it on ‘Do not disturb.’”

Stéphane Bancel was hobnobbing with the world’s richest and most powerful people, hoping to win an edge for his 10-year-old biotechnology company, Moderna. 

During breaks in the four-day World Economic Forum conference, when there was no one to glad-hand, the native Frenchman sat in a 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 outbreak of pneumonia was tearing through a city there. Their crude bars just kept getting longer and longer. 

Bancel had to pull out his iPad to look up the unfamiliar city: Wuhan. Then he saw its size and its many daily airplane routes. And he knew.

Despite Chinese assurances the disease was under control, Hatchett, Farrar and Bancel realized this was the epidemic they’d anticipated – and feared – for years. 

Bancel called his staff in Cambridge, Massachusetts, and told them to ramp up work they had just begun to consider developing a candidate vaccine against COVID-19. 

“We need to think bigger. This is not an outbreak. This could be a pandemic a la the 1918 Spanish Flu,” Bancel told them. “They thought I was crazy.” 

Roger Connor had been spending a lot of time on the phone with his boss, the London-based CEO of GlaxoSmithKline, Emma Walmsley. They usually talked a few times a week. Lately it had been every day.

Connor had recently spoken to Hatchett, the head of CEPI, who told him the Chinese situation could be a “globally significant outbreak.” 

That caught Connor’s attention. The Northern Ireland native already was running a crisis team for GSK, looking after employees in China affected by the disease.

“This was a real moment that made us think we need to look at other scenarios,” said Connor, who oversees GSK’s 17,000-person Global Vaccines division from his base in Brussels. 

During his call with Walmsley on Jan. 24, Connor started brainstorming what solutions GSK could offer a global community soon to be overwhelmed by this new virus.

“We are the biggest vaccine player in the world. We’ve been involved in pandemics previously. We knew that we had to be a part of the solution,” Connor said.

The pair reviewed GSK’s potential vaccine technologies. But Connor and Walmsley concluded they could best hedge their bets by pursuing an adjuvant, rather than a vaccine.

An adjuvant adds punch. It allows vaccines to be used in lower doses, preserving a precious resource. It makes vaccines work better in people with weaker immune systems, like those 65 and older, who account for 80% of COVID-related deaths in the U.S. 

And an adjuvant can be used with a variety of vaccines, so if one fails – as about two-thirds of vaccine candidates eventually do – a GSK product could still find a market. One that called for selling 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 Health and Human Services Secretary Alex Azar on his left.

Interspersed with other government officials, pharmaceutical executives such as Walmsley and Bancel delivered elevator pitches about what they were doing to fight the pandemic. 

Trump seemed concerned with one thing: How soon can you get a vaccine ready? Faster than the others? 

John Shiver of Sanofi said his company’s candidate vaccine could be delivered to the first person maybe in about a year. “Difficult to predict, Mr. President, knowing that a vaccine has to be both safe and efficacious because it’s given to healthy people,” he said. 

Stanley Erck, CEO of Novavax, pledged to start much sooner, with a small Phase 1 trial by May or June. Inovio promised to launch one in April.

Moderna’s Bancel said he was ready to start any day; he was just waiting for a government sign-off.

“You won’t have a vaccine. You’ll have a vaccine to go into testing,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, cautioned after Bancel spoke.

Delivering a shot into a few shoulders as part of a trial was very different from being able to inject hundreds of millions of Americans with a safe, effective vaccine. 

Trump focused on the shortest time frames when summarizing what he’d heard “That’s tremendous news. And I think the speed is a lot greater than a lot of people would have thought,” said Trump, who used some version of the word “quick” 10 times during the hour-long meeting. 

As the meeting neared its end, a reporter asked: “Is it realistic to think, really, that a vaccine could be ready in three or four months?”

“Well, you have the greatest companies in the world sitting around the table,” Trump responded. “I mean, Johnson & Johnson and Pfizer and all of the companies … you have all of these great companies and that’s what they’re saying. So I think that —”

Fauci interjected. Someone needed to get the president an explainer on the steps involved to get a vaccine to market for the general public.

“Would you make sure you get the President the information that a vaccine that you make and start testing in a year is not a vaccine that’s deployable?” Fauci implored. “That is going to 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 quickly injected the candidate vaccine, mRNA-1273, developed by Moderna and the federal government.

The vaccine, like others, takes aim at the spike protein on the outside of the coronavirus. But the technology is new, employing a genetic messenger that tells a person’s own cells to create the virus’s signature protein, causing their body to recognize and fight the invader. 

The approach is innovative and quick – and never has produced an approved product. 

The shot marked the launch of the first human trials against COVID-19, the start of Phase 1. It had been only 63 days since the publication of the virus’ genetic sequence.

“There’s no doubt that that’s the world indoor record,” Fauci said later. “I’ve never seen anything go that fast.”

Dr. Philip Dormitzer had taken aim at novel viruses before: the 2009 swine flu and the 2013 H7N9 flu. But he’d never had the red carpet rolled out like this.

Whatever he needed to pursue SARS-CoV-2, all he had to do was ask.

“Our CEO Albert Bourla said very early on, do whatever you need to do to succeed at this. If you need a resource just ask for it, and you’ll get it,” said Dormitzer, chief scientific officer for viral vaccine R&D with the pharmaceutical giant Pfizer, Inc.

If he needed to transport samples, suddenly the corporate jet and helicopters were available. 

“I’ve always had to justify everything I was doing in the budget,” said Dormitzer, who made the leap into drug companies after a dozen years as an infectious disease pediatrician, mostly at Harvard University. “That’s a level of support I’ve just never quite experienced before. I shouldn’t get used to it.”

While he’d known people who caught the flu in 2009 and 2013, it was nothing like what was happening as winter turned into spring in the New York City region where he lives and works.

He was blown away, he said, at the dedication of the 350 employees who showed up at Pfizer’s Pearl River facility every day, wearing masks, propping doors open so they wouldn’t have to touch handles, and working as fast as they could to get a vaccine ready for human testing.

Like other companies, Pfizer executives weren’t sure at first whether they should pursue a COVID-19 vaccine. 

The vaccine industry had learned a lesson from previous near-pandemics like SARS, MERS, Ebola and flu: Many burn out on their own or with public health measures. That’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 wrestled with a fundamental question: Could the company financially justify developing a vaccine against it?

The answer came from the daily news. The bar graphs that Bancel had started drawing on napkins only six weeks earlier were soaring. 

Unlike SARS or MERS, many people infected with SARS-CoV-2 weren’t sick enough to quickly retreat to bed. They were more likely to pass on 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 variations of the same mRNA technology that Moderna was using. The trial included 13 different groups, with 15 volunteers in each. Some got a placebo, others different doses of the potential vaccines.

“We were lucky,” Dormitzer said. The two vaccines most viable to produce at scale also showed good results. 

Both looked 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 people use to learn about vaccine development and production.

If you’d asked him in February how long it would take to get a vaccine candidate ready for clinical trials, he would have said at least a couple of years.

Now he was trying to prove himself wrong. 

Srivastava, a native of India, runs Sanofi’s Protein Sciences site in Meriden, Connecticut. He helped develop the innovative flu vaccine that triggered Sanofi’s purchase of Protein Sciences in 2017.

More than 80% of the flu vaccine made in the U.S. every year is grown in chicken eggs – hundreds of millions of them. The process takes about six months, which means the strains used in the vaccine have to be chosen more than half a year ahead of flu season, although the flu virus mutates constantly.

They mutate so much that the strains put into the eggs are sometimes not the ones that come out, which may be one reason the flu vaccine isn’t always highly effective.

Srivastava and his team got around that problem by growing the flu vaccine with the help of an insect virus rather than eggs, substantially cutting development time.

Now, Sanofi wanted him to grow the SARS-CoV-2 spike protein in the same bug virus. 

His team started rotating shifts, seven days a week, wearing personal protective gear and keeping as physically distant as possible in the lab.

Technicians ran each of the normal steps as quickly as they carefully could, working in parallel instead of the usual sequence. They chose materials they could easily buy at large scale. 

They added the spike protein’s DNA to the bug virus and grew it in a giant bioreactor, purifying the results.

Running the process took nine days from start to finish. Any mistake would set them back at least a week. 

Srivastava said he spent several rough nights wondering what he would do if it didn’t work. “I couldn’t really find an answer to my own question,” he said.

But with a small team focused on each major step, they needed just two batches to show their process worked. They produced enough material for a Phase 1 study and laid out plans for the much larger Phase 3 they hoped would follow. 

“It was a technology we understood well,” said Shiver, global head of R&D for vaccines at Sanofi.

On April 11, BARDA gave Sanofi the go-ahead to proceed with Phase 1; on the 14th, Sanofi and GSK signed a deal to combine Sanofi’s vaccine with GSK’s adjuvant.

Though so many people felt helpless against the pandemic, Shiver said Sanofi employees working on the vaccine felt empowered.

“We’re in a unique position to actually do something,” Shiver said.

Nicholas Kartsonis, like many others in vaccine development, had been working seven days a week for months. 

Kartsonis and his team at Merck screened thousands of compounds to see if they might make effective vaccines. They had reviewed 250 possible partnerships with other companies to develop a vaccine. 

As other companies began testing their candidate vaccines in people and collecting billion-dollar promises from the federal government, Merck was still at the drawing board.

Finally, by the end of April, they’d narrowed their options to two vaccines. One, dubbed v590, was based on a similar vaccine Merck had licensed to fight Ebola.

That vaccine, approved last year, used a virus common in cows to carry the spike protein into human cells. “We understood the manufacturing processes,” said Kartsonis, who leads infectious disease clinical research from Merck’s West Point, Pennsylvania site, a 45-minute drive north of Philadelphia.

If Merck could make a vaccine as effective against COVID-19 as that one was against Ebola, he said, it would outshine its competitors. With the Ebola vaccine, 95% of those vaccinated were protected for at least three years.

Plus, since the virus that delivers the vaccine makes copies of itself inside the human body, one dose should be enough to protect against COVID-19. All the other vaccines backed by U.S. funding will require two shots each. 

Merck’s second candidate vaccine, v591, also replicates in the body, so one dose should be protective. It’s based on a collaboration with Austria’s Themis Bioscience. 

“We’d really like to have a single-dose vaccine,” Kartsonis said, noting that both of his candidates are based on “tried and true, proven platforms,” while his competitors are using technology that is more novel. “We really wanted to do something that would supplement what others were doing.”

All 7.7 billion people on the planet can’t be protected with a single vaccine. Using vaccines that work differently increases the chances of protecting everyone, from children to pregnant woman to the aging seniors who fare so badly when they catch COVID-19.

Merck still hasn’t gotten a commitment from the federal government to fund manufacturing, but the week before Memorial Day, the threads Kartsonis had been working on for months finally started to come together. After the holiday weekend, Merck closed a deal to buy Themis and gain control over v591. It signed a collaborative agreement to develop v590, and another to develop an antiviral.

Merck wouldn’t be 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 will be the first person to do a happy dance in my office,” Kartsonis said, though it would be behind closed doors, he added, because his dancing isn’t fit for public viewing.

He doesn’t care which company gets a vaccine first. Kartsonis just hopes the pharmaceutical industry, which doesn’t have the best public reputation, gets to show it can make a positive difference in the world. 

“I want my kids to go back to school like everybody else does, irrespective of whether it’s Merck or not Merck.”

A little before 7 a.m., television anchor Dawn Baker rolled up her sleeve, baring her upper arm. The needle that jabbed her contained a dose of the candidate vaccine developed by Moderna and Fauci’s agency.

It had to be kept very cold, but not at minus 94 degrees Fahrenheit, as it had earlier in the research. This marked a triumph for the scientists who had struggled to make their product more stable so it would remain effective when stored in a normal freezer rather than at the temperature of dry ice.

Baker, an anchor at CNN affiliate WTOC in Savannah, was the first of 30,000 people in the Phase 3 study, half of whom would get the active vaccine and half a placebo.

She told a CNN interviewer she hoped to become a role model – as a trial participant and as a Black woman in that trial. 

“I have heard a lot of friends of mine and even relatives who said that, you know, ‘I won’t be the first person to get this vaccine. I don’t want to be the guinea pig. I’m going to wait and see what happens first,'” Baker told viewers. “I hope that maybe just seeing my face will help them to change their opinions.”

A few hours later, Fauci and Dr. Francis Collins, head of the National Institutes of Health, held a news conference touting the start of the Phase 3 trial. 

Collins described the research as “a big American opportunity for people to come on board as our partners, to try to take part in what has been a historic effort to bring to an end the worst pandemic our world has seen in over 100 years.”

Later that afternoon, Pfizer quietly announced that it, too, had begun a 30,000-person Phase 3 trial.

Speaking on state television, Russian President Vladimir Putin announced that a Moscow-made vaccine had been approved for general use. “It has passed all the necessary tests,” he said.

He declared that Russia had won the race for a vaccine.

The shot was named Sputnik-V, recalling the Soviet Union’s Sputnik satellite, which surprised the world in 1957 when it became the first man-made object to successfully orbit the earth.

Scientists outside Russia were skeptical. There simply hadn’t been enough time to produce a vaccine and test it in thousands of people.

“Not sure what Russia is up to but I certainly would not take a vaccine that hasn’t been tested in Phase III,” Florian Krammer, professor of vaccinology at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, said on Twitter. “Nobody knows if it’s safe or if it works.”

By another measure, China had already won.

In June, the Chinese government announced it had begun widespread vaccination of military service members – essentially conducting a trial on its soldiers – though little is confirmed and it’s not clear whether anyone will be studying their reactions.

Every Friday afternoon, Dr. Macaya Douoguih’s team at Janssen Vaccines holds a video conference to update one another on their progress. 

“It’s been really good news for many consecutive weeks,” said Douoguih, who beams in from her home office in The Hague. “So far we haven’t seen any surprises – no, ‘Oh God, this is a setback!’”

Douoguih, who went to medical school at the University of Washington, heads clinical development and medical affairs at Janssen Pharmaceutical Companies of Johnson & Johnson, whose offices are based in Leiden, about 12 miles from her home.

The work has been nonstop since March, she said. Creating a coronavirus vaccine is both a sprint and a marathon.

“It’s one of those things where at a certain point you realize, ‘Wow. I’m really tired,’ and you just spontaneously start crying,” Douoguih said.

Then she goes go back to work.

Under her direction, Phase 1 and 2 trials are underway and she is anticipating Phase 3 trials to begin later this month.

Sanofi and GSK recently launched a 440-person combined Phase 1-2 trial in the U.S. Merck’s v591 is in Phase 1 and v590 will be there soon. The company, which has received only $38 million in federal money so far, hopes bigger subsidies won’t be far behind.

Day to day, the vaccine makers themselves don’t know how their candidate is faring. The data is “blinded” until it meets certain milestones.

After rushing at breakneck pace for months, Douoguih, Srivastava, Kartsonis and other vaccine developers have to sit on their hands and wait for trial results.

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 protected] and Elizabeth Weise at [email protected]

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.