For most people, some already on their third or fourth messenger RNA coronavirus shot from Moderna or Pfizer-BioNTech, it’s a puzzle: A new vaccine? Now? Why bother?
But for a small contingent of holdouts who have closely tracked the progress of the Novavax vaccine, this is a long-awaited moment of truth.
“Some people can’t take the mRNA vaccines, and it’s important to have a choice,” said Victoria Dawson, 74, of New York, who is allergic to an ingredient in the mRNA shots. She received a Johnson & Johnson shot and booster but hopes her next shot will be from Novavax.
“I’m being very cautious. I’m staying around my apartment complex and not eating in restaurants,” Dawson said. “I get up in the morning and just stress the minute I get up.”
Even though Novavax lost the race to be first, company executives argue that their shot will help fill in the margins of the pandemic vaccination campaign and play an important role in helping people live alongside the virus into the future.
They argue that their vaccine, which can stay stable at refrigerator temperatures long-term and may be better tolerated than alternatives, will have key advantages once the exigencies of the pandemic recede. But hopes were dashed Friday that the vaccine would offer an alternative for people worried about rare heart inflammation associated with mRNA vaccines. An FDA review found that there were five cases of inflammation, mostly in men, within two weeks of being vaccinated in the company’s trials, “raising concern for a causal relationship.”
The Novavax vaccine is poised to hit the U.S. market as more than three-quarters of people 18 and older are already fully vaccinated. Among the unvaccinated, some may be waiting for another option, but others may not be interested at all. Novavax plans to seek expanded authorization for use of the shot in adolescents and as a booster.
An agency review released Friday said that testing and submission of manufacturing information about the vaccine was “still in process” and would be essential “to ensure the vaccine’s quality and consistency for authorization.” A meeting of Centers for Disease Control and Prevention vaccine advisers, a critical step before a vaccine becomes available, has not been scheduled yet. The company plans to have shots ready to supply “within a very short period of time” — a few weeks after the FDA authorizes the shot, said John Trizzino, chief commercial officer at Novavax.
Despite the late arrival of their vaccine, Novavax executives remain confident it will fill a need.
“If you would have asked anybody in the space 12 months ago what would be happening in the pandemic now, they would have said, ‘Oh, by now we’d be long past the pandemic,’ ” Trizzino said.
In a brightly lit laboratory in Gaithersburg, Md., a cloudy, yellowish broth swirls inside Erlenmeyer flasks. The glass containers, shaking back and forth inside two incubators, are teeming with cells from a pest known as the fall armyworm moth.
Those moth cells are tiny vaccine factories, churning out coronavirus spike proteins found in the newest omicron subvariants, BA.4 and BA.5. Even as Novavax scientists wait for their first-generation vaccine to be authorized — based on earlier versions of the virus — they are working on new formulations to be ready for wherever the pandemic swerves next.
The winding path to this moment — a vaccine on the cusp of authorization a year after it was shown to be 90 percent effective — underscores the speedy development of the first vaccines. The time lag for the Novavax vaccine reflects a combination of factors: the more time-consuming technology used in the company’s shot; the growing pains of a small company that had to expand quickly; and manufacturing delays.
What makes Novavax’s vaccine attractive to some people — that it’s an older, more familiar technology — is also what made it trail other shots. Protein-based shots are tried and true — they’re used against influenza, hepatitis B and shingles. But the timeline to develop them is longer.
The newer mRNA vaccines instruct cells inside the body of vaccine recipients to build the coronavirus spike protein. The J&J shot uses a harmless virus to spur cells to churn out the spike protein. Novavax, by contrast, manufactures and purifies the coronavirus spike proteins in a laboratory.
Novavax scientists start with a baculovirus, which in nature infects insects. The baculovirus is engineered to carry genetic instructions for building the coronavirus spike protein. The baculovirus, with its genetic instructions, is then introduced into cells taken from the fall armyworm moth. In progressively larger vessels, researchers brew a cloudy broth of moth cells capable of churning out the spikes. In a factory in India, where manufacturing takes place, there are 6,000-liter stainless steel vats teeming with the insect cells.
To recover the key vaccine ingredient, the coronavirus spike proteins, scientists purify and filter out other cellular debris. Then, they add detergent to create a spike-covered soap bubble that looks similar to the virus itself. An adjuvant, a vaccine ingredient that revs up the immune system, is added.
Gale Smith, Novavax’s chief scientist, said he started working on the technology in the early 1980s as a graduate student.
“I had this crazy idea when I was a graduate student,” Smith said, talking over the loud hum of lab equipment. “I knew it was important, and I can tell you — hardly anyone shared that opinion.”
The advantage of “bug cells,” as Smith calls them, is that they are adept at making complex proteins.
Still, cool science alone can’t get a vaccine across the finish line, and at the beginning of the pandemic, Novavax started out with disadvantages. The biotech company had never launched a vaccine. Its staff had been slashed and key manufacturing capabilities sold off to keep the company afloat after efforts to develop a vaccine against RSV — respiratory syncytial virus — foundered in 2016.
Novavax’s coronavirus vaccine was one of six candidates backed by Operation Warp Speed, the federal program to accelerate vaccine development. The government invested $1.6 billion in the Maryland company to support development of the shots. Even with the influx of cash, the challenges of scale-up were enormous.
“We weren’t a developed company at that time. We started with 100 people in the U.S., without any laboratory space at the time,” chief executive Stanley C. Erck said. “Starting Jan. 12, 2020, we had seven-day weeks for two years. Every day, we’d work to get to the next experiment, to the next data point.”
The Novavax workforce exploded during the past two years to 1,600 employees, and a new headquarters is under construction. The growth is visible in every department. At a glassed-in corridor, scientists receive frozen patient samples from vaccine trials around the world.
Last year, a staff of nearly 60 received and analyzed results from about 100,000 samples. So far this year, they’ve analyzed 87,000 and are looking to expand the lab to double their capacity by next year.
The Serum Institute of India is manufacturing Novavax’s vaccine, and U.S. regulators needed to inspect that plant, which added to the time it took to review the company’s application for FDA authorization, Erck said.
Novavax also lost time in manufacturing because of difficulties with tests used to check the contents and quality of the vaccine. Vaccine makers must demonstrate to regulators that their product is consistent in every batch and every vial.
“That can take a long time — to both get that process right and to the level of purity the FDA requires,” said Kathleen M. Neuzil, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine.
The company filed for emergency authorization in January.
With more than three-quarters of U.S. adults fully vaccinated, few people expect that a fourth shot will significantly boost vaccination rates. For Novavax executives, one of their selling points has been the promise of helping to close the vaccine hesitancy gap, but the experience in some European countries, where the shot is available, has not borne that out.
There is a niche group of people in the United States who connect on social media and who have been holding out for the shot because they can’t or won’t take existing vaccines. But the shot’s true potential is global or as a booster. It has been approved in more than 40 countries. And if it is eventually authorized in adolescents and children, that could also spur greater use.
“I still think there are quite a lot of people who are nervous about the mRNAs, all these people who haven’t gotten boosted. I think there’s a niche there for people who feel safer with” the Novavax shot, said Kathryn Stephenson, a vaccine expert at Beth Israel Deaconess Medical Center in Boston who led a Novavax trial.
With the virus continuing to throw curveballs, adding another option to the arsenal could be crucial for the future, experts said.
Some people had hoped the protein shot might be an attractive option in a world in which there are choices, especially because mRNA shots have been associated with a risk of heart inflammation in younger men. But the five cases of heart inflammation identified in Friday’s FDA review “support a concern for causal relationship to vaccine,” FDA reviewers wrote.
Novavax took issue with the FDA analysis, arguing that the rates of heart inflammation were exceedingly low and were the same in the vaccine and placebo groups. “We believe there is insufficient evidence to establish a causal relationship,” the company said in a statement.
For Randy Cox, 42, of Ludington, Mich., the revelation that the same rare heart risk may exist with this vaccine as with mRNA vaccines comes as a major disappointment.
For months, Cox has been waiting on Novavax because he is fearful that mRNA vaccines — with their rare potential to cause heart inflammation in men — could exacerbate the baseball-size cyst on the right atrium of his heart. As much of the country was vaccinated, boosted and even boosted again with mRNA vaccines, Cox kept his mask on and continued wiping down his groceries.
“It comes as quite a shock” to learn about heart inflammation associated with the Novavax shot, Cox said.
He had been frustrated by the slowness of the regulatory review and watched with envy as other countries authorized the vaccine. When Canada authorized the Novavax shot, Cox applied for a passport, thinking he could make the five-hour drive — only to learn that people who weren’t Canadian citizens couldn’t just roll up their sleeves and get a shot.
Now, Cox said he is going to have to dig into the data, watch the FDA meeting and think about whether he still wants Novavax, or whether — if the risks are about the same — he would settle for the Pfizer-BioNTech vaccine that has been more widely used.
“I’m really bummed,” Cox said.