You’ve never heard of the Covid booster with the fewest side effects

The first time I got a Novavax Covid vaccine, it felt almost subversive. 

Over the previous few years, every mRNA-based booster I’d gotten — the ones made by Moderna and Pfizer — had felt like a two-day bout of the flu. I’d gamely booked sick days into my calendar and sucked it up through fevers, headaches, and exhaustion, comforting myself with ibuprofen and the knowledge that at least I was keeping my elderly parents safe.

Two and a half years into the pandemic, the Food and Drug Administration approved a Covid vaccine made by biotech company Novavax using older vaccine production technology. Licensed for people 12 and over, it was nearly as effective at Covid prevention as Pfizer and Moderna’s mRNA vaccines — and, as I noted with great interest, it had fewer side effects. In 2023, I got one. 

The difference was staggering: Although I felt a little weak and shaky for a few hours on the night of my injection, I woke up the next morning feeling blissfully normal, with only a mild soreness in my arm and a smug pep in my step. This year, there was no question what I’d do — it would be easy, breezy Novavax for me.

More than half of all people who get mRNA boosters have similar unpleasant short-term side effects to mine. But strangely, few of them seem to see Novavax as an alternative: As of August, Americans had received 650 million mRNA vaccine doses, compared with only 83,000 Novavax doses. Experts told me Novavax has suffered both from its timing and from an unearned reputation as a dark horse. “There’s this perception that this is some kind of second-line vaccine that people take if they don’t want to get the mRNA vaccines,” says Amesh Adalja, an infectious disease doctor and senior scholar at the Johns Hopkins Center for Health Security, “but it should not be.”

“They’re equivalent, and there may be some advantages to getting it,” he told me.

Although the worst of the pandemic is long over, there are still plenty of good reasons to get a Covid-19 booster. The virus caused more than 76,000 deaths in 2023 and nearly 41,000 hospitalizations between October 2023 and last April. There’s still a risk of developing long Covid after infection, even if it is lower than during the earliest days of the pandemic.

Still, more than half of Americans don’t plan to get a Covid booster this year, according to a recent Pew Research Center survey, and the discomfort they cause is a big reason why. Sixty percent of people not lining up for a shot said side effects were a major reason for their disinterest. 

Maybe more people would get Covid boosters if they knew what I know about Novavax: Making the smart choice for your and your community’s health doesn’t have to feel like crap.

Why nobody thinks of Novavax first

Novavax is built differently from other Covid vaccines, which is part of why it didn’t enter our vaccine vocabularies until later in the pandemic.

The Moderna and Pfizer vaccines — the first Covid immunizations the FDA approved in December 2020 — were created using technology that had previously only been used in clinical trial settings. The technology involves encoding genetic blueprints for the novel coronavirus’s spike protein onto fragile mRNA molecules and delivering them to the body’s muscle cells to produce an immune response. 

Like the mRNA vaccines produced by Moderna and Pfizer, Novavax was created to combat Covid-19. Unlike them, it’s based on older technology that mirrors methods used to produce many other conventional vaccines that have been around for decades. 

It takes a lot longer to create a vaccine that uses conventional technology. That explains why the first version of Novavax wasn’t approved until August 2022, almost two years after mRNA vaccines came on the market. It is also only approved for older children (age 12 and up) and adults. 

“In general, the first to the market tends to have a lot of advantage in terms of uptake,” Adalja says. Novavax’s later release means many people may simply not think about it when they think of Covid vaccines.

Novavax has less severe side effects than either of the mRNA vaccines

Before mRNA vaccines were even approved by the FDA, it was clear their short-term effects were more severe than those of other vaccinations that had come before. In early reports, participants in vaccine trials reported severe fatigue, headache, and muscle and joint pains that simply didn’t happen with other vaccines.

With time, more data emerged. The vaccines had been split into two doses given a number of weeks apart. In vaccine trials, many adults had short-term side effects beyond sore arms, especially after the second dose. Their symptoms included fatigue (60 percent to 65 percent), headache (50 percent to 60 percent), and fever (11 percent to 15 percent) lasting for one to two days. For both the Moderna and Pfizer vaccines, post-vaccination symptoms were more common in children and adolescents, and less common in adults 65 and older. 

(Notably, anywhere from a quarter to half of people who received a saline placebo instead of either Pfizer or Moderna vaccine also reported these symptoms, except fever — so it’s not entirely clear how much of the vaccine group’s discomfort was due to the vaccine.) 

Once the general public started getting the vaccines, the full extent of these side effects became clearer. Fatigue, headache, or muscle aches occurred after the second injection in about half of people who participated in a voluntary vaccine safety tracking system, while a quarter to a third of those people had chills, fever, or joint pain. In one study, 37 percent of healthcare workers who got the vaccines were sick enough in the following couple of days that they had to miss work.

When Novavax came on the scene a little less than two years after the mRNA vaccines rolled out, a large study suggested it would have milder side effects. In particular, fever was less common among people who got the vaccine, occurring in only 6 percent of people after a second dose. Other side effects were also less frequent, and all went away faster than the symptoms that followed mRNA vaccines — after a matter of hours rather than days.

“There are a lot of people that are legitimately knocked out for a couple of days with the mRNA, and you’re not going to get that with Novavax.”

There’s no big head-to-head comparison study of both mRNA vaccines and Novavax to quantify just how big the differences in their side effects are. However, a small Chinese study published earlier this year hints at just how much more tolerable Novavax is than its mRNA counterparts. Among people who got the current versions of the Novavax and Pfizer vaccines in late 2022, those who got the Pfizer mRNA vaccine were six times as likely to have fever and more than three times as likely to have chills and muscle aches. Only 2 percent of people in the Novavax group had each of these symptoms; the only symptom they reported more often than the Pfizer group was fatigue.

Kirsten Lyke, an infectious disease doctor and vaccine researcher at the University of Maryland School of Medicine, led a safety study on mixing and matching brands of initial Covid vaccines and booster doses. Although the study wasn’t designed to compare the side effects of different vaccines, it was clear people who got Novavax booster doses had milder side effects that resolved more quickly than those boosted with mRNA vaccines. 

“There are a lot of people that are legitimately knocked out for a couple of days with the mRNA, and you’re not going to get that with Novavax,” she says.

Novavax works as well as mRNA vaccines

So Novavax causes fewer annoying side effects than other vaccines. How well does it protect you from Covid?

When the mRNA vaccines first became available in late 2020, the yardstick experts used to communicate their quality was their effectiveness at preventing infection. At the outset, Moderna’s and Pfizer’s vaccines had 95 percent vaccine effectiveness, which meant that among 100 people at risk of catching the virus, they kept all but 5 of them from getting infected.

Novavax was tested at a different time, after the virus had evolved, and many people had already been exposed to Covid-19. Its initial effectiveness was measured at 90 percent.

The current evidence suggests that people initially vaccinated with mRNA vaccines who go on to get a Novavax booster are well covered — in Lyke’s study, they developed antibody levels well above the level needed to protect people from Covid. Although mRNA boosters may lead to higher antibody levels, “higher isn’t necessarily better,” she says.

Other studies have suggested the antibodies Novavax elicits may hang around longer than the ones other vaccines provoke; still others indicate that when it comes to more real-world outcomes like developing symptoms after infection, Novavax is as good as any other vaccine on the market. 

Those studies are from 2021 and 2022, and involved Covid variants that are different from the ones circulating now. More recent assessments of how good the newest version of Novavax is at preventing Covid infection and severe illness — like the data the FDA reviewed before approving the 2024-2025 version of the Novavax booster — are from studies in mice, not humans. Still, they suggest the latest editions of Novavax are in the ballpark of its earlier versions when it comes to protecting us from the virus’ worst. You can check the Novavax website to find a pharmacy near you where you can get a Novavax vaccine.

Fundamentally, it’s time to stop worrying about whether one vaccine is slightly more effective at preventing certain outcomes than others, says Lyke. “At this point, we’re kind of beyond that,” she says. “We have a lot of options and you can pick and choose,” she says, “and you’re probably not going to make a wrong decision.”