Is the Novavax COVID Vaccine Better than mRNA Vaccines? What We Know So Far

As the updated COVID vaccines roll out around the country, one more competitor has joined the mix. In early October the U.S. Food and Drug Administration authorized a new booster shot made by the company Novavax. Like the mRNA-based Pfizer and Moderna shots, it targets a SARS-CoV-2 variant, XBB.1.5, which is a descendant of Omicron. It is the first protein vaccine to appear in more than a year, which some public health experts say is encouraging news for people who are hesitant the mRNA vaccines that have been widely used throughout the pandemic.

Scientific American consulted experts on the latest science behind the new shot.

What’s different about Novavax’s vaccine?

Unlike Moderna’s and Pfizer’s mRNA vaccines, which contain modified viral genetic material that the body’s own cellular machinery uses to make viral proteins that elicit an immune response, Novavax relies on a more traditional approach in which proteins resembling those in SARS-CoV-2 are injected directly into the body. This protein-based method has been used for more than 30 years in other vaccines, such as the hepatitis B vaccine. The company Novavax produces the protein in moth cells, which grow more quickly than mammalian cells.

The Novavax jab also includes a proprietary compound called Matrix-M, which was developed from the bark of Chilean soapbark trees and further stimulates the immune system. Matrix-M is now being integrated into other vaccines, including one for malaria that the World Health Organization approved earlier this month.

What variants does it target?

The new Novavax vaccine was developed for the XBB.1.5 viral variant—the same one targeted by Moderna’s and Pfizer’s updated shots. None of these are optimized for newer versions of the virus, including the Eris and Pirola variants that became prominent in August and appear better able to escape the immune system than previous mutants. (The FDA selected the XBB.1.5 variant for this fall’s boosters in June). That’s nothing new, says vaccinologist Gregory Poland of the Mayo Clinic—vaccine companies have been “chasing the tail” of emerging variants throughout the pandemic, he says.

All three vaccine boosters seem to confer at least some protection against the new variants. But one disadvantage of protein vaccines is that it takes much longer for researchers to develop new formulas to protect against new variants, whereas mRNA vaccines can be adapted far more easily.

How effective is it?

Novavax has about the same efficacy as other COVID vaccines, says infectious disease researcher Kirsten Lyke of the University of Maryland. A study published this month found that the Novavax booster was about 55 percent effective at preventing COVID symptoms and 31 percent effective at preventing infection, which is similar to the mRNA vaccines.

Lyke’s own July study in the journal npj Vaccines tested whether “mixing and matching” the different COVID vaccine and booster types produced stronger or more durable immunity against the virus. It found that all the boosters led to similar antibody responses regardless of whether a person had initially received an mRNA or protein vaccine. Other evidence published in 2022 suggested that receiving an mRNA booster after a protein vaccine, such as Novavax’s original shot or the now-discontinued Johnson and Johnson protein subunit vaccine, might produce the best immunity of all.

According to Lyke’s most recent study, the antibodies elicited by the new Novavax booster may have lasted a little longer than those produced after an mRNA vaccine. But Lyke says that’s not conclusive: by the time the study began early in 2022, many vaccinated people had recently been infected with Omicron or another dominant variant that’s good at avoiding the immune system. The infection gave their body a level of natural immunity that was difficult to distinguish from the vaccine’s effects.

Lyke says it is nearly impossible to directly compare different vaccines’ efficacy, given that people have had different exposures, infections and combinations of vaccinations. “I just don’t think we can run those trials anymore,” she says.

What are the side effects?

Compared with mRNA vaccines, the Novavax booster seems to have a lower risk of causing myocarditis or pericarditis—heart conditions that occasionally occur, especially in young men—although it does not have zero risk. It also has fewer side effects, including muscle fatigue and nausea, in the first 48 hours after vaccination. “If people have had a side effect with an mRNA vaccine, I’d say try a protein subunit [vaccine],” Poland says. “The goal is to get you protected.”

But it is difficult to draw firm conclusions on the vaccines’ comparative safety. “We’ve got millions of data points for the mRNA vaccine, and we don’t have that for Novavax,” Poland says. Manufacturing issues prevented the company’s immunization against the original COVID variant from being approved until 2022—long after most people who wanted a vaccine had gotten one. The CDC estimates that fewer than 90,000 doses of the original Novavax vaccine were administered, and only a few hundred people have received the booster in clinical trials.

When will Novavax be available for the fall and winter season?

Novavax says the booster is now available in pharmacies and that it has shipped millions of doses to thousands of locations around the country. Like the mRNA vaccines, the Novavax booster is one dose, but the CDC recommends that unvaccinated people receive two doses eight weeks apart.

The rollout of the latest round of boosters—both the mRNA and protein varieties—has lagged despite rising numbers of COVID infections in recent weeks. This has largely been because of confusion around how the vaccines would be paid for after the U.S. government announced it would no longer pay for all COVID vaccines and instead mandated all insurance companies to cover them for free. Some areas won’t have boosters available right away as states continue to navigate insurance and delivery complications. But no matter which vaccine booster becomes available first, Lyke says, the most important thing is to “pick one and get it.”

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