The mRNA Vaccines Are Extraordinary, but Novavax Is Even Better

 Persistent hype around mRNA vaccine technology is now distracting us from other ways to end the pandemic.

By Hilda Bastian   The Atlantic

JUNE 24, 2021

Alastair Grant / AP

At the end of January, reports that yet another COVID-19 vaccine had succeeded in its clinical trials—this one offering about 70 percent protection—were front-page news in the United States, and occasioned push alerts on millions of phones. But when the Maryland-based biotech firm Novavax announced its latest stunning trial results last week, and an efficacy rate of more than 90 percent even against coronavirus variants, the response from the same media outlets was muted in comparison. The difference, of course, was the timing: With three vaccines already authorized for emergency use by the U.S. Food and Drug Administration, the nation is “awash in other shots” already, as the The New York Times put it.

Practically speaking, this is true. If the FDA sees no urgency, the Novavax vaccine might not be available in the U.S. for months, and in the meantime the national supply of other doses exceeds demand. But the asymmetry in coverage also hints at how the hype around the early-bird vaccines from Pfizer and Moderna has distorted perception. Their rapid arrival has been described in this magazine as “the triumph of mRNA”—a brand-new vaccine technology whose “potential stretches far beyond this pandemic.” Other outlets gushed about “a turning point in the long history of vaccines,” one that “changed biotech forever.” It was easy to assume, based on all this reporting, that mRNA vaccines had already proved to be the most effective ones you could get—that they were better, sleeker, even cooler than any other vaccines could ever be.

But the fascination with the newest, shiniest options obscured some basic facts. These two particular mRNA vaccines may have been the first to get results from Phase 3 clinical trials, but that’s because of superior trial management, not secret vaccine sauce. For now, they are harder and more expensive to manufacture and distribute than traditional types of vaccines, and their side effects are more common and more severe. The latest Novavax data confirm that it’s possible to achieve the same efficacy against COVID-19 with a more familiar technology that more people may be inclined to trust. (The mRNA vaccines delivered efficacy rates of 95 and 94 percent against the original coronavirus strain in Phase 3 trials, as compared with 96 percent for Novavax in its first trial, and now 90 percent against a mixture of variants.

Read: The differences between the vaccines matter

Pandemic-vaccine success, as I wrote last year, was never just about the technology. You needed a good vaccine, sure—but to get it out the door quickly, you also had to have a massive clinical-trial operation going, and it had to be situated in places where the virus would be spreading widely at just the right time. Even if your candidate worked amazingly well, if you weren’t testing it in the middle of a huge outbreak, you’d have to wait a very long time for the evidence to build.

The precise timing of these studies mattered a great deal in practice. The Phase 3 clinical trials for Pfizer and Moderna, for example, were up and running in the U.S. by late summer 2020, and so they caught the nation’s giant wave of infections in the fall. By the time Novavax had finished recruiting in the U.S. and Mexico, in February, case rates had been dropping precipitously. This fact alone, independent of any aspect of vaccine technology, did a lot to shape the outcome.

Corporate strategy was another crucial factor. To “win” the vaccine race, a company would need to be able to produce high-quality vaccine doses reliably and quickly, and in vast numbers. It would also need to field the challenges of working with multiple regulatory agencies around the world. And it would need to do all of this at the same time.

BioNTech, the German company that developed the Pfizer mRNA vaccine, could not have accomplished so much, so quickly by itself. Last October, the company’s CEO, Uğur Şahin, told German interviewers that BioNTech had sought out Pfizer for help because of the scale of the clinical-trial program necessary for drug approvals. That strategic partnership, and not simply the “triumph of mRNA,” was what propelled them past the post. (Moderna had the advantage of its partnership with the National Institutes of Health.) Consider this: The BioNTech-Pfizer first-in-human vaccine study appeared on the U.S. government’s registry of clinical trials on April 30, 2020—the same day as the first-in-human vaccine study for Novavax, which would be going it alone. In a parallel universe where Novavax had paired up with, say, Merck, this story could have come out very differently.

In the meantime, the early success of two mRNA vaccines pulled attention away from the slower progress of other candidates based on the same technology. Just two days after last week’s Novavax announcement came the news that an mRNA vaccine developed by the German company CureVac had delivered a weak early efficacy rate in a Phase 3 trial, landing below even the 50 percent minimum level set by the World Health Organization and the FDA. “The results caught scientists by surprise,” The New York Times reported. CureVac is the company that President Donald Trump reportedly tried to lure to the U.S. early in the pandemic, and the one that Elon Musk said he would supply with automated “RNA microfactories” for vaccine production. In the end, none of this mattered. CureVac’s mRNA vaccine just doesn’t seem to be good enough.

The “sobering” struggles of CureVac perfectly illustrate what epidemiologists call “survivor bias”—a tendency to look only at positive examples and draw sweeping conclusions on their basis. When the Pfizer and Moderna vaccines triumphed, The Washington Post suggested that a bet on “speedy but risky” mRNA technology had paid off with a paradigm-shifting breakthrough. Anthony Fauci called the gamble “a spectacular success.” Such analyses usually had less to say about the non-mRNA vaccines that had gotten into clinical trials just as quickly—and about the other mRNA vaccines that were hitting snags along the way.

Now we’ve seen what happened to CureVac, and that some mRNA formulations clearly work much better than others. By one count, nine groups were testing mRNA COVID-19 vaccines in animal studies as of May 2020, and six were expected to be in clinical trials a few months later. By the end of the year, only BioNTech-Pfizer, Moderna, and CureVac had reached Phase 3 testing, compared with 13 non-mRNA vaccines. Of the nine mRNA-vaccine candidates that were already testing in animals in mid-2020, just two have proved efficacy at this point, while no fewer than nine vaccines based on more traditional technologies have reached the same mark.

These other, non-mRNA vaccines have been widely used throughout the world—and some could still make an important difference in the U.S. Although the U.S. has plenty of doses of the Pfizer and Moderna vaccines available right now, demand for them has cratered. The Washington Post reports that in 10 states, fewer than 35 percent of American adults have been vaccinated. An international study of COVID-19 vaccine misinformation, published in May, found that among the most common online rumors were those alleging particular dangers of mRNA technology—that it leads, for example, to the creation of “genetically modified human beings.” The CDC has also made a point of debunking the circulating falsehood that COVID-19 vaccines can change your DNA. For a time, it looked as though the Johnson & Johnson vaccine would help address this worry. It’s based on a fairly new technology, but not as new as mRNA. However, concerns about tainted doses made at a Baltimore factory and the emergence of a very rare but serious side effect have pretty much dashed that hope. The Johnson & Johnson single-dose vaccine has reportedly accounted for fewer than 4 percent of doses administered in the country.

Read: Microchipped vaccines, a 15-minute investigation

In this context, the success of the Novavax vaccine should be A1 news. The recent results confirm that it has roughly the same efficacy as the two authorized mRNA vaccines, with the added benefit of being based on an older, more familiar science. The protein-subunit approach used by Novavax was first implemented for the hepatitis B vaccine, which has been used in the U.S. since 1986. The pertussis vaccine, which is required for almost all children in U.S. public schools, is also made this way. Some of those people who have been wary of getting the mRNA vaccines may find Novavax more appealing.

The Novavax vaccine also has a substantially lower rate of side effects than the authorized mRNA vaccines. Last week’s data showed that about 40 percent of people who receive Novavax report fatigue after the second dose, as compared with 65 percent for Moderna and more than 55 percent for Pfizer. Based on the results of Novavax’s first efficacy trial in the U.K., side effects (including but not limited to fatigue) aren’t just less frequent; they’re milder too. That’s a very big deal for people on hourly wages, who already bear a disproportionate risk of getting COVID-19, and who have been less likely to get vaccinated in part because of the risk of losing days of work to post-vaccine fever, pain, or malaise. Side effects are a big barrier for COVID-vaccine acceptance. The CDC reported on Monday that, according to a survey conducted in the spring, only about half of adults under the age of 40 have gotten the vaccine or definitely intend to do so, and that, among the rest, 56 percent say they are concerned about side effects. Lower rates of adverse events are likely to be a bigger issue still for parents, when considering vaccination for their children.

Don’t get me wrong—the Pfizer and Moderna vaccines have been extraordinary lifesavers in this pandemic, and we may well be heading into a new golden age of vaccine development. (This week, BioNTech started injections in an early trial for an mRNA vaccine for melanoma.) But even the best experts at predicting which drugs are going to be important get things wrong quite a bit, overestimating some treatments and underestimating others. Pharmaceuticals are generally a gamble.

But here’s what we know today, based on information that we have right now:  Among several wonderful options, the more old-school vaccine from Novavax combines ease of manufacture with high efficacy and lower side effects. For the moment, it’s the best COVID-19 vaccine we have.

The Atlantic’s COVID-19 coverage is supported by grants from the Chan Zuckerberg Initiative and the Robert Wood Johnson Foundation.

Hilda Bastian is a scientist, writer, and founding member of the Cochrane Collaboration. She was formerly the editor of the PubMed Health project at the National Library of Medicine.

Source

The Differences Between the Vaccines Matter

 Yes, all of the COVID-19 vaccines are very good. No, they’re not all the same.

By Hilda Bastian   The Atlantic      

MARCH 8, 2021

Adam Maida / Getty / The Atlantic

Public-health officials are enthusiastic about the new, single-shot COVID-19 vaccine from Johnson & Johnson, despite its having a somewhat lower efficacy at preventing symptomatic illness than other available options. Although clinical-trial data peg that rate at 72 percent in the United States, compared with 94 and 95 percent for the Moderna and Pfizer-BioNTech vaccines, many experts say we shouldn’t fixate on those numbers. Much more germane, they say, is the fact that the Johnson & Johnson shot, like the other two, is essentially perfect when it comes to preventing the gravest outcomes. “I’m super-pumped about this,” Virginia’s vaccine coordinator told The New York Times last weekend. “A hundred percent efficacy against deaths and hospitalizations? That’s all I need to hear.”

The same glowing message—that the COVID-19 vaccines are all equivalent, at least where it really counts—has been getting public-health officials and pundits super-pumped for weeks now. Its potential value for promoting vaccination couldn’t be more clear: We’ll all be better off, and this nightmare will be over sooner, if people know that the best vaccine of all is whichever one they can get the soonest. With that in mind, Vox has urged its readers to attend to “the most important vaccine statistic”—the fact that “there have been zero cases of hospitalization or death in clinical trials for all of these vaccines.” The physician and CNN medical analyst Leana Wen also made a point of noting that “all of the vaccines are essentially a hundred percent” in this regard. And half a dozen former members of President Joe Biden’s COVID-19 Advisory Board wrote in USA Today, “Varying ‘effectiveness’ rates miss the most important point: The vaccines were all 100% effective in the vaccine trials in stopping hospitalizations and death.”

There’s a problem here. It’s certainly true that all three of the FDA-authorized vaccines are very good—amazing, even—at protecting people’s health. No one should refrain from seeking vaccination on the theory that any might be second-rate. But it’s also true that the COVID-19 vaccines aren’t all the same: Some are more effective than others at preventing illness, for example; some cause fewer adverse reactions; some are more convenient; some were made using more familiar methods and technologies. As for the claim that the vaccines have proved perfectly and equally effective at preventing hospitalization and death? It’s just not right.

These differences among the options could matter quite a bit, in different ways to different people, and they should not be minimized or covered over. Especially not now: Vaccine supplies in the U.S. will soon surpass demand, even as more contagious viral variants spread throughout the country. In the meantime, governors are revoking their rules on face masks, or taking other steps to loosen their restrictions. It’s tempting to believe that a simple, decisive message—even one that verges on hype—is what’s most needed at this crucial moment. But if the message could be wrong, that has consequences.

The idea that all of the vaccines are pretty much the same, in that they’re perfect at preventing COVID-19 hospitalizations and death, got its legs on social media. The USA Today op-ed by the former members of the Biden team illustrated this by linking to a data table found on Twitter. Created by the infectious-disease doctor Monica Gandhi, it showed a variety of trial results for six different vaccines. One column was rendered in canary yellow—“Protection from hospitalizations/death”—and every cell read “100%.” A similar table, tweeted out a few days earlier by the dean of Brown University’s School of Public Health, Ashish Jha, conveyed the same idea through a grid of zeros—as in, zero people hospitalized, zero people dead. The prominent physician and researcher Eric Topol followed with his own clinical-trial data summary featuring a column of 100 percents. “That is impressive!” he wrote across the top. All told, their posts would be retweeted about 15,000 times.

The data were indeed suggestive of an encouraging idea. Based on the numbers so far, we can expect the vaccines to provide extremely high levels of protection against the most dire outcomes. Still, we don’t know how high—and it’s clear they won’t uniformly cause hospitalizations and deaths from COVID-19 to disappear in vaccinated people.

The experts understand this, of course. Gandhi has been updating her table as more data come in, and now pegs Moderna’s efficacy on that front at 97 percent; Jha has since tweeted that “nothing is 100 percent … But these vaccines sure are close”; and Topol told The Atlantic that the numbers in his tweet are not a sufficient basis from which to draw “any determination of magnitude of effect,” though the fact that they all point in the same direction is “very encouraging.” Still, the message of perfection that their initial tables and tweets spawned—the gist, for many readers, of all those 100s and zeros—has since been picked up far and wide, and misinterpreted along the way.

To grasp the shaky nature of these particular data, it’s important to remember how the vaccine-development process began. Last April, not long after the pandemic began, the World Health Organization set out a target efficacy for vaccines of 50 percent, with options for how that value should be measured. A vaccine could be shown to reduce the risk of symptomatic disease, severe disease, or transmission of the coronavirus. The FDA offered similar guidance in June, and other regulatory agencies also followed the WHO’s lead. Among these choices, symptomatic disease was the most feasible, because it’s both a common outcome and one that’s easier to confirm in a large-scale trial. An outcome that included asymptomatic infections would have been even more common, but screening for all infections would have been prohibitive, especially early in the pandemic. So that’s how the vaccine trials were designed: Each would try to demonstrate at least 50 percent efficacy with respect to symptomatic disease as its “primary outcome.”

The trials could have used severe disease, hospitalization, or death as primary outcomes, but that would have slowed things down. These events are far more infrequent—there could have been 200 infections for each COVID-19 death in the U.S.—and that means it would have taken more time, and larger numbers of trial participants, to generate enough data to be sure of a 50 percent efficacy. Developers did include “severe COVID-19” as a secondary outcome—that is, one that would be measured and analyzed, but for which the trial might not have been designed to provide a definitive answer. Efficacy against hospitalization and against death, however, were not included as secondary outcomes for every trial.

Given that fact, the data can’t support a claim that the vaccines are 100 percent effective at preventing these serious outcomes. (Topol highlighted this very issue in an op-ed last fall for The New York Times.) Out of the six vaccines included in the dramatic data tables that made the rounds on Twitter, the clinical trials for only two of them—Oxford-AstraZeneca’s and Johnson & Johnson’s—included hospitalization for COVID-19 as a secondary outcome, and reported that efficacy rate. The clinical research for one other vaccine, made by Novavax, had hospitalization as a secondary outcome, but that trial hasn’t been reported in full yet. (On my website, I’ve provided more detailed information and analysis of the relevant data.)

Now, a casual reader of clinical-trial reports—or their summaries on social media—might take the fact that no hospitalizations of vaccinated people are mentioned to mean that none occurred. That’s risky, given that pieces of the data have been published across various medical journals and via several different regulatory agencies rather than in full in one place; that the plans for some trials did not specify ahead of time that the vaccine’s efficacy at preventing hospitalizations would be calculated; and that we’ve seen only minimal early data (via a press release from Novavax) from one of them. It would be just as risky to assume that all hospitalizations would be included in the analyses of people who developed severe COVID-19. Hospitalization and severe disease are not synonymous—people could be coping at home even though COVID-19 has caused their oxygen levels to drop severely, and moderately ill people might be hospitalized out of an abundance of caution when they are at high risk of getting worse.

The two vaccine trials that did explicitly report hospitalizations as an efficacy outcome make this latter issue very clear. For the AstraZeneca vaccine, one person in the control group had severe COVID-19, but eight people were hospitalized; for Johnson & Johnson, 34 people in the placebo group had severe COVID-19, but only five people were hospitalized. It’s true that zero vaccinated people were hospitalized in either study after the vaccines took effect. But with numbers that small, you can’t draw a reliable conclusion about how high efficacy may be for these outcomes. As Diana Zuckerman of the National Center for Health Research pointed out about the Johnson & Johnson trial, “It’s misleading to tell the public that nobody who was vaccinated was hospitalized unless you also tell them that only 5 people in the placebo group were hospitalized.” She’s right. And you can’t be confident about predicting effectiveness precisely in a wider population outside the trial, either. For example, some of the vaccine trials included relatively few people older than 60 as participants.

You can see how fragile these numbers are by looking at those compiled for severe disease. In the Pfizer trial, for example, just one vaccinated person developed severe COVID-19 versus three in the placebo group—which meant that a single bout of disease made the difference between a calculated efficacy rate of 66 percent and one of 100 percent. For the Novavax and Oxford-AstraZeneca trials, there were zero people with severe disease in the vaccinated group versus only one in the control group, so adding or subtracting one would have been even more dramatic. The problem is even greater for deaths. For that efficacy analysis, only two of the vaccine trials—for Moderna’s and Johnson & Johnson’s—reported any COVID-19 deaths at all in the control groups.

It’s also important to remember that these are early results: Some people who enrolled very late in the trials aren’t yet included in reported data, and analysis is still under way. Indeed, the FDA pointed out in December that one vaccinated person in the Moderna trial had been hospitalized with apparently severe COVID-19 two months after receiving a second dose. That person was in a group still awaiting final assessment by the researchers, and was not mentioned in Moderna’s formal readout of results.

We’ve learned a little more from the ongoing public vaccination programs. Four important reports have come in the past two weeks. In one, researchers compared about 600,000 people who had had a full course of the Pfizer vaccine in Israel with 600,000 people matched in age and other demographics who had not been vaccinated. The shots’ effectiveness at preventing hospitalization was measured at 87 percent. (“This vaccine is fabulous in a real world setting,” Jha tweeted in response.) A preprint from Scotland reported an efficacy rate against hospitalization of about 80 percent among people 80 or older, almost all of whom had received only one dose of either the Pfizer or the AstraZeneca vaccine. Two reports from Public Health England estimated a reduction of hospitalization of about 50 percent and 43 percent for the same age group, again almost all after just one dose of the Pfizer vaccine. These are exciting outcomes—those vaccines really, really worked! But they oughtn’t lead anyone to think that the vaccines are all the same, and that protection will be perfect.

---

Where does that leave us for making decisions? As Anthony Fauci told The New York Times last weekend, “Now you have three highly effective vaccines. Period.” Again, you will get a lot of benefit from any of them, and your risk will shrink even more as those around you get vaccinated too. Whichever one you start with, a booster may be coming in the not-so-distant future, of the same vaccine or perhaps a different one. By taking the first vaccine you can get, you’ll also avoid the risk of finding yourself without protection if infection rates surge where you live.

Efficacy is merely one layer, though. The Pfizer and Moderna vaccines have an edge at preventing symptomatic illness, but the Johnson & Johnson vaccine brings its own advantages. It has no demanding freezer requirements, which means it’s easier to distribute and more accessible to many communities. It’s more affordable than the other two—the company is providing it at cost around the world. Then there’s the fact that resources can be stretched a lot further when only a single dose has to be administered.

For individuals, too, the Johnson & Johnson vaccine has benefits. As a one-and-done injection, it’s more convenient. It also has a lower rate of adverse events than Moderna’s. You can’t compare results of these trials too precisely, but there are indications of a striking difference. About 2 percent of those who got the Johnson & Johnson vaccine recorded having reactions, such as fatigue, muscle aches, and fever, that were severe enough to interfere with daily activities. For those getting their second injection of Moderna, that rate was higher than 15 percent. People who are on the fence about getting vaccinated may find that this difference tips the scales in favor of getting a shot. Others who have doubts about the newness of the mRNA technology in the Pfizer and Moderna vaccines may appreciate the fact that Johnson & Johnson’s approach has already been deployed in the company’s Ebola vaccine, which got full drug approval in Europe last year.

Given these concerns, there’s some danger in the message—however well intentioned—that the COVID-19 vaccines are all the same by any measure, or that they’re perfect wards against severe disease. Vaccination is a public-health imperative, and going full tilt to promote uptake supports the common good. But it’s a personal health decision too. People want to protect themselves and those close to them, and they are likely to care about outcomes other than hospitalization and death, no matter what anyone says now.

Still, raising these concerns in public can be fraught. In response to an inquiry about her data table, Gandhi affirmed the importance of looking at severe-disease outcomes and noted that “careful, collegial and collaborative scientific discourse on the vaccines is imperative moving forward to help us get through the pandemic.” Topol pointed out that he has emphasized the vaccines’ measured efficacy against symptomatic disease many times before, so any isolated reference to his table “takes that particular post out of context.” Jha wrote in an email that he stands by the message of his original tweet, and notes that COVID-19 hospitalizations and deaths are so rare among the people vaccinated in these trials, to quibble over differences is akin to “counting how many angels are dancing on the head of the pin.”

I can see why this might seem like quibbling, but I just don’t think it’s a trivial matter. It would be different if I thought the effectiveness of every one of those six vaccines against hospitalizations and death would really end up being close to 100 percent—or if I bought into the idea, now widespread, that they have already been shown to “nearly” or “effectively” eliminate these outcomes. There is very good reason to be encouraged by the data, but to say right now that people who have been vaccinated face zero risk of serious outcomes—that, for them, COVID-19 is no more dangerous than the common cold—is sure to influence behavior. Imagine how people in high-risk groups would feel about going to the movies, or how their employers would feel about putting resources into workplace safety, if we all assumed that vaccines confer perfect protection against hospitalization or death. Now imagine how the same people and employers would feel knowing they were 85 percent protected.

Nor is there any reason to believe that the public or the personal interest will be served by hype. People who think the vaccines provide ironclad protection may lose trust in experts if reality falls short. Trust in coronavirus-vaccine information is already a problem, and could sink even lower. Activists who are opposed to vaccination may end up turning experts’ “super-pumped” promises against them.

“The idea that people can’t handle nuance,” Jha tweeted at the end of February, “it’s paternalistic. And untrue.” I couldn’t agree more. The principle of treating people like adults is fundamental. We don’t need to exaggerate. Talking about the trade-offs between different medicines and vaccines is often complicated, but we do it all the time—and we can do it with COVID-19 vaccines too.

Hilda Bastian is a scientist, writer, and founding member of the Cochrane Collaboration. She was formerly the editor of the PubMed Health project at the National Library of Medicine.

Twitter

MOST POPULAR

1. How Long Does Omicron Take to Make You Sick?

   The new variant seems to be our quickest one yet. That makes it harder to catch with the tests we have.

   KATHERINE J. WU

   

2. Omicron Is the Beginning of the End

   No matter the severity of the variant, the appetite for shutdowns or other large-scale social interventions simply isn’t there.

   YASCHA MOUNK

   

3. Fully Vaccinated Is About to Mean Something Else

   The CDC might update the definition very soon, even though we still don’t know for sure how many shots we’ll need.

   KATHERINE J. WU

   

4. Omicron Is Our Past Pandemic Mistakes on Fast-Forward

   We’ve been making the same errors for nearly two years now.

   KATHERINE J. WU, ED YONG, AND SARAH ZHANG

   

5. Don’t Be Surprised When You Get Omicron

   America is in for a lot more breakthrough infections. Here’s what to do if you fall sick.

   YASMIN TAYAG

   

6. 
   

14 Jun 21 Novavax vaccine shows 90% efficacy

Powerful new COVID-19 vaccine shows 90% efficacy, could boost world’s supply

By Meredith WadmanJun. 14, 2021 , 6:00 AM

A participant in Plano, Texas, is injected during Novavax’s North American COVID-19 vaccine trial this spring. The company reported its results today.

 

NOVAVAX

The dark horse vaccine company Novavax announced strong results today from a pivotal, 30,000-person trial of its pandemic coronavirus vaccine in the United States and Mexico. The vaccine uses a protein of SARS-CoV-2, a different technology from the COVID-19 vaccines authorized so far, and delivered 90.4% overall efficacy against symptomatic COVID-19 infections, and 100% protection against moderate and severe disease. Against eight viral variants of interest and concern, its efficacy was 93.2%. And the vaccine appeared safe and well-tolerated.

“This vaccine looks phenomenal. I am thrilled about these results,” says Monica Gandhi, an infectious disease physician and epidemiologist at the University of California, San Francisco. She notes that the clinical trial was highly diverse, with 44% nonwhite participants, and that the vaccine’s straightforward storage requirements could speed access to it in remote communities around the globe.

The difference of a few percentage points between Novavax’s 90% efficacy and the 95% and 94% efficacy of the Pfizer-BioNTech and Moderna vaccines is explained in part by Novavax’s later trial, which pitted the vaccine against viral variants, says John Moore, an immunologist at Weill Cornell Medicine and a participant in the Novavax trial. The trials of those other companies’ vaccines, composed of messenger RNA (mRNA), were completed before such variants were widely circulating.

“This is a vaccine whose efficacy is at least on a par with Pfizer and Moderna,” Moore says. “It’s essentially 100% protective against disease.”

One expert is less impressed, however. “The data they have [are] nothing spectacular,” says Vijay Samant, CEO of Xiconic Pharmaceuticals and former chief operating officer of Merck’s vaccine division. “The efficacy overall is couple of notches below the Pfizer and Moderna studies. … It’s a me-too vaccine at best.”

Novavax plans to apply to the U.S. Food and Drug Administration and other regulators for an emergency use authorization in the third quarter, once the company completes regulatory requirements aimed at ensuring its product consistently matches the vaccine used in the clinical trials, said President and CEO Stanley Erck.

Today’s announcement marks the end of a very long beginning for the once-moribund Gaithersburg, Maryland, company, which began to develop a vaccine in January 2020 and that July won $1.6 billion from the U.S. government’s Operation Warp Speed. But the company encountered production problems that delayed the launch of its North American clinical trial until late December 2020.

In the trial, two-thirds of participants at 113 sites in the United States and six sites in Mexico initially received two doses of the vaccine separated by 21 days. One-third of participants received a placebo. Between 25 January and 30 April, participants experienced 77 cases of COVID-19, 63 of them in the placebo group. All 14 cases in vaccinated participants were mild.

These results are similar to those Novavax reported in January from a late-stage trial of more than 15,000 people in the United Kingdom. That trial showed the vaccine efficacy was 89% overall, 86% against the Alpha variant that was first identified in the United Kingdom, and 96% against the original virus strain. But in a separate trial involving 4400 participants in South Africa, where the worrisome Beta variant arose and was circulating widely, the vaccine’s overall efficacy sank to 49%.

In the new trial, Novavax sequenced 70% of all the coronaviruses that caused illness. In more than half of the sequenced cases, they found the culprit was the Alpha variant, which accounted for 70% of U.S. infections by late April. But the company did not provide specific efficacy data against Alpha or any other variant. (Only two cases of the Beta variant were reported in the trial.)

“It doesn’t really address the lingering questions about how well the vaccine would work against ‘escape’ variants” such as Beta, says Natalie Dean, a biostatistician at the University of Florida.

The COVID-19 vaccines so far authorized by major Western regulatory agencies deliver genetic material that directs a recipient’s cells to make spike, a surface protein from SARS-CoV-2, that then trains the immune system to respond to the virus. Novavax’s vaccine instead delivers the spike protein itself, carried on soaplike particles and given extra punch by an immune-boosting substance called an adjuvant. Protein technology has been used for decades in vaccines against diseases including hepatitis B.

In clinical trials so far, Novavax’s vaccine has produced somewhat fewer powerful, though transient systemwide side effects such as headache, muscle pain, and fatigue, which many recipients of the Pfizer-BioNTech and Moderna vaccines experienced. For instance, 54% of participants who received Moderna’s vaccine as part of a 30,000-person trial reported at least one such effect; in Novavax’s 15,000-person trial in the United Kingdom, that number was 38%.

After a second dose of vaccine in the North American Novavax trial, about 40% of participants who received the active vaccine reported experiencing some degree of headache, muscle pain, or fatigue. But serious reactions were rare.

Having relatively mild side effects is a plus, says Mayank Mamtani, a biotechnology analyst who follows Novavax for B. Riley Securities. “This Novavax vaccine is going to be less reactogenic. You don’t have to cancel all your meetings” afterward, he says. He adds that the Novavax jab may find a niche as a booster vaccine in the United States, where he says such boosters may be needed by October or November. “We in this country love choice,” he adds.

Under its 2020 contract with Operation Warp Speed, Novavax committed to deliver 110 million doses to the U.S. government, although the country does not need them for initial vaccinations. Novavax expects to reach manufacturing capacity of 100 million doses per month by the end of the third quarter and 150 million doses per month by the fourth quarter of this year, Erck said.

The company has advance-purchase orders for about 200 million doses from another five Western governments and last month signed a deal to supply Gavi, the Vaccine Alliance, with 350 million doses for the COVID-19 Vaccines Global Access (COVAX) Facility, a global vaccine-sharing partnership. The Serum Institute of India, which is also making the Novavax vaccine, is slated to deliver another 750 million doses to COVAX, Novavax says. Serum plans to start delivering the Novavax vaccine by September, provided regulatory agencies have authorized it, officials there told Science.

Novavax’s production projections are substantially dialed back from earlier company predictions that it would ship 2 billion doses this year. That reflects the company’s struggle to scale up its manufacturing both at its own facilities and those of contractors and partner companies in 11 nations. “Novavax has been particularly challenged with executing on production scale-up efforts and manufacturing,” Mamtani wrote in a note to investment clients last month.

Unlike mRNA vaccines, which need to be stored frozen, Novavax’s protein vaccine can be stored in a refrigerator for up to 6 months, and, once removed, remains viable for 24 hours. Novavax has created a new version of its vaccine, adapted to the Beta variant, that could be used as a 1-year booster, the company says. On Friday, it announced positive results for the adapted vaccine in mice and baboons. Novavax says it is also working to customize its vaccine to other SARS-CoV-2 variants.

But Samant cautions that Novavax’s manufacturing struggles and the entrenched advantages of companies whose vaccines were approved months ago may make the small company’s climb to market share and profitability a tough one.

Posted in: 

• Health
• Coronavirus

doi:10.1126/science.abj7408

Related

• 

  Biden adds voice to calls for further investigation into origins of pandemic virus

• 

  Antivaccine activists use a government database on side effects to scare the public

• 

  Rich countries cornered COVID-19 vaccine doses. Four strategies to right a ‘scandalous inequity’

See all of our coverage of the coronavirus outbreak

https://www.sciencemag.org/news/2021/06/powerful-new-covid-19-vaccine-shows-90-efficacy-could-boost-worlds-supply