Novavax, a Maryland biotechnology company that endured delays in developing a coronavirus vaccine, revealed results Monday showing that the world is close to having another shot that prevents illness and death, stops virus variants — and proves easy to store.
Vaccinated people were completely protected against severe and even moderate cases of illness. There were no cases of hospitalization or death among people who received the vaccine. The shots also may be the most tolerable yet tested. Side effects included fatigue, headaches and muscle pain, but reactions tended to be less frequent than those triggered by some already authorized vaccines.
“It’s really very impressive,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, noting the vaccine was on par with the most effective shots developed during the pandemic. “It’s very important for the world’s population to have, yet again, another highly efficacious vaccine that looks in its trial to have a good safety profile.”
Kathleen Neuzil, professor of vaccinology at the University of Maryland School of Medicine, said she often cautions people not to compare vaccine trials because there are so many differences in how and when they are conducted.
“Once you get to 90 to 100 percent effective, it’s hard to even decipher differences. … The efficacy looks great,” Neuzil said. “We need the manufacturing, obviously, to get it to the world.”
The good news comes with a caveat: The vaccine may not begin to have a large impact on the pandemic until late summer or fall.
Stanley C. Erck, Novavax’s chief executive, said in an interview that Novavax will apply for regulatory clearance from a half-dozen countries in the third quarter, which begins in July. It has an inventory of tens of millions of doses and plans to scale up to manufacturing 100 million doses a month by the end of September. The company said it expects to hit its target of 150 million doses a month in the last three months of the year.
In the United States, Novavax still needs to file for emergency authorization. The data, which was presented in a news release, will be examined by regulators at the Food and Drug Administration and by an external committee of vaccine advisers. Erck said the U.S. process may take longer than elsewhere in the world, and he anticipated the vaccine will have its biggest initial impact globally, through the World Health Organization’s Covax initiative.
“A lot of our vaccine is going to be targeted in the early stages for Covax … and so a lot of those doses are going to get into the low- and middle-income countries first, which is a good thing,” Erck said. Novavax has pledged 1.1 billion doses to Covax.
The Novavax vaccine was one of six candidates the U.S. government made a huge bet on, investing $1.6 billion to pay for research and development and preorder 110 million doses.
The decision to back Novavax — a 34-year-old Gaithersburg, Md., company that has never pushed a vaccine across the finish line and had to sell off its manufacturing facilities to stay financially afloat months before the pandemic hit — raised eyebrows.
Then early tests showed that Novavax’s vaccine triggered an impressive immune response, generating high levels of virus-fighting antibodies capable of blocking the pathogen from invading cells. In January, the vaccine made a big splash when a large United Kingdom trial showed it was nearly 90 percent effective — even once a more transmissible variant had taken hold.
Over the past five months, the world has impatiently waited on the next steps — confirmatory evidence from a U.S. trial twice as large as the U.K. study, regulatory okays and the delivery of hundreds of millions of doses badly needed to help end the pandemic.
The U.S. trial, originally intended to launch in October, did not start until the last days of December, in part because of manufacturing delays. By then, people in the United States were becoming eligible for authorized vaccines. Novavax pushed back its timelines as it worked on manufacturing steps, including laboratory tests to show its product is consistent and potent.
Meanwhile, the United States secured more than enough shots from the three companies with authorized vaccines — Pfizer-BioNTech, Moderna and Johnson & Johnson — to satisfy demand. A fourth, from AstraZeneca, reported results in March.
As the course of the pandemic changed, Novavax began formulating a new version of its vaccine against a particularly worrisome variant and devising strategies in which its vaccine might be used as a booster. A small South African trial suggested that vaccine efficacy dropped against the variant that emerged there, but there were only two cases caused by that variant noted among the people who fell sick in the North American trial.
“When I hear people talk about us being fifth, I’m always thinking: There’s never been a need in the vaccine world … like this,” Gregory Glenn, president of research and development for Novavax, said in an interview before the results were released.
“I live in the United States, and one of the upsides we’re starting to see are some glimmers of hope that life could get back to normal,” said Glenn, noting the resources needed to accomplish that and the remaining need in much of the world. “That’s our push,” Glenn said. “Our push is a global push.”
The Novavax vaccine uses a traditional technology, with some novel twists.
Recombinant protein vaccines such as Novavax’s — the hepatitis B vaccine is another — have been used for decades. They teach the immune system to recognize a virus by presenting a laboratory-made version of a viral protein.
Novavax uses insect cells originally harvested from the ovaries of the fall army worm and grows enormous numbers of those cells in giant bioreactors. Scientists use a baculovirus, which infects insect cells, to insert the genetic instructions for the coronavirus spike protein. The insect cells produce the proteins, which are extracted and purified. The proteins form nanoparticles and are paired with an extract from the soapbark tree that grows in Chile that acts as an adjuvant, revving the immune system.
The company had to rely on external research and development firms to scale up its process. Some of its first doses were made by Emergent BioSolutions, but because that company was making other vaccines for Operation Warp Speed — the Trump administration initiative to expedite coronavirus vaccines and treatments — Novavax then moved to Fujifilm Diosynth Biotechnologies in North Carolina.
The company has built a global manufacturing network through partnerships with pharmaceutical firms and purchased a factory in the Czech Republic to supply the world and meet its intended production target of 2 billion doses in a year. Takeda Pharmaceutical in Japan plans to manufacture 250 million doses. GlaxoSmithKline intends to make up to 60 million doses for the United Kingdom.
Once the production process is in place, the vaccine offers potential advantages. Its manufacturing process is familiar to vaccine manufacturers and its deployment in the field is relatively simple because it can be stored in a refrigerator, several scientists said.
“The benefit of their formulation … is it’s remarkably scalable, so they can scale to a very high number of doses,” said Matthew Frieman, a coronavirus expert at the U-Md. School of Medicine who began collaborating with the company in 2012, on a vaccine for a different coronavirus, Middle East respiratory syndrome. “It’s not a super-strange production platform … you don’t need super-specialized facilities. It’s stable, so you don’t need severe cold chain” to store the vaccine.
Fauci said the success of so many vaccines is a testament to the years of work into finding ways to stabilize coronavirus spike proteins, which was led by researchers at NIAID’s Vaccine Research Center and the University of Texas at Austin. Novavax, like Pfizer-BioNTech, Moderna and Johnson & Johnson, integrated tiny genetic changes to the blueprints for the spike protein churned out by the insect cells, to make sure they stayed in the right shape to teach the immune system how to recognize the virus.
Andrew Ward, a structural biologist at the Scripps Research Institute and one of the co-inventors of alterations to the spike protein, said once the manufacturing and purification steps are worked out for Novavax’s vaccine, the process can be replicated in factories throughout the world.
Longer term, the addition of another vaccine with a different technology could add a new element to the vaccine landscape: competition and price pressure.
“This should actually put some pricing pressure, as well, when governments are buying lots of vaccine and have choices,” Ward said. “The more players on the market is going to drive the cost down.”