Your Next COVID Vaccine May Have a New Formulation Aimed at XBB.1.5 Variant

COVID-19 vaccines are on track to get an upgrade. A panel of independent advisors to the Food and Drug Administration (FDA) voted unanimously Thursday to recommend that vaccines be updated to target emerging subvariants of Omicron.

The currently-available vaccines are bivalent, meaning they target two strains of COVID-19—the original virus and the Omicron subvariants that dominated last winter. BA.4 and BA.5 have now faded into the background and the bivalent vaccines are not nearly as protective against new variants.

The new monovalent vaccines would target one subvariant of Omicron, called XBB.1.5. This variant now accounts for about 40% of new U.S. COVID cases.

“We’re concerned that we may have another wave of COVID-19, the virus may further evolve, the immunity of the population has declined further, and we move indoors for wintertime,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, during the panel.

Drugmakers Pfizer, Moderna, and Novo Nordisk said they could have the new XBB.1.5-specific formulas ready by the end of the summer.

Why Vaccines Need an Upgrade

More than nine months of clinical and real-world data show that the bivalent vaccines targeting BA.4 and BA.5 are better at protecting against Omicron than the original monovalent vaccine was. But it’s also become clear that the longer it’s been since a person’s last shot, the less protected they’re likely to be.

Besides, the bivalent vaccines are not very potent against current circulating strains. The XBB lineages have evolved about as far from Omicron as Omicron BA.5 was from the original COVID-19 strain.

The Centers for Disease Control and Prevention (CDC) said people who have received a bivalent booster dose within the last two months are about 62% protected against hospitalization from COVID-19. But among those who have gone up to six months without a booster shot, the vaccine efficacy drops to 24%. When only considering the last few months, when XBB has dominated, the bivalent shot was even less effective.

Still, the vaccines appear to continue to protect against critical illness, like admission to the intensive care unit and death, even among people with immunocompromising conditions.

What the Vaccine Rollout May Look Like

The FDA previously told Americans to expect a new COVID-19 vaccine to protect against new variants each fall, in line with flu shots. But the panel disagreed over committing to that plan.

Some members said that aligning the updated COVID-19 vaccine campaign with the flu campaign would increase vaccine uptake. So far, 17% of Americans have received the bivalent booster shot. Public health officials could launch one, aggressive campaign to get Americans vaccinated against respiratory diseases this fall, and people could get appointments for both shots in one visit.

While that may make for a convenient public health response, it’s not yet clear if COVID-19 will be a seasonal virus this year. While there are often spikes in cases during the winter, there have also been outbreaks in every other season throughout the pandemic.

Scientists now know that the best time to get a COVID-19 vaccine is right before an uptick in disease, said panelist Ruth Link-Gelles, PhD, MPH, a senior epidemiologist at the CDC. Unfortunately, outbreaks are nearly impossible to predict.

“This season will be telling, in terms of whether COVID-19 settles into a seasonal pattern or not,” Link-Gelles said.

Some panelists were equally concerned about committing to an updated vaccine strategy for the future before knowing what the cadence of COVID-19 seasons will be.

“Using the word ‘season’…links the campaign to influenza vaccine. I understand it may be convenient and most efficient to give the vaccines together, but it’s only been a few years—we don’t know what the COVID season is and it may ultimately confuse people about when and where to get the vaccine and how frequently,” said panelist Mark Sawyer, MD, FAAP, a panelist and professor of clinical pediatrics at the University of California San Diego School of Medicine.

Nevertheless, it takes time to design and manufacture new vaccines, and sticking to a fall rollout is reasonable for this year, Marks said.

“In order to make a few hundred million doses of vaccine, essentially, practically, we’re going to have one update per year,” Marks said. “Barring some new major development that requires agile public health response, we’re dealing with a vaccine that will be used in 2023 through to 2024.”

Marks said it’s likely that an updated vaccine would be ready for rollout around September.

What’s in the Proposed Vaccine?

XBB is a recombinant of two BA.2 derived viruses, BA.2.10.1 and BA.2.75. The subvariants that are dominating U.S. cases include XBB.1.5, XBB.1.16, and XBB.1.9.1.

Each of the vaccine manufacturers created a new formulation that targets XBB.1.5. Pre-clinical data from each company indicate that this vaccine appears to be effective against the other XBB variants, too, likely because they’re so genetically similar.

Moderna tested how well a vaccine including both the original COVID-19 strains and XBB.1.5 performed. Pfizer tried a vaccine targeted at XBB.1.5 and BA.4 and BA.5.

The monoclonal version with just one strain outperformed each of the bivalent options. That’s likely because the vast majority of people have already seen the original strain, either through vaccination or infection, panelist Jerry Weir, PhD, director of the Division of Viral Products at the FDA Center for Biologics Evaluation and Research, said.

A monovalent version of the Novavax vaccine, which uses a recombinant protein technology, performs on par with its mRNA counterparts.

Where Vaccination Efforts Stand

About 74% of Americans older than 5 have completed their primary COVID vaccine series, and only about a fifth of adults have gotten a booster shot.

“We have to do better because we have not done a good job today communicating to the American public what’s going on here,” Marks said. “They’re still not getting these vaccines in the way we’d like to potentially see people—even those over the age of 65—get vaccinated.”

The public health emergency for COVID-19 has ended. However, Marks said the FDA still has the power to grant new formulations of the COVID-19 vaccine emergency use authorization (EUA). He also said the agency is working towards fully licensing the COVID-19 vaccines through the fall.

James Hildreth, PhD, MD, a panelist and president of Meharry Medical College emphasized the importance of ensuring that people can continue to access the COVID-19 vaccines free of charge, now that the public health emergency has ended.

The FDA is working to simplify the immunization schedule, especially for children 4 and under, said panelist David C. Kaslow, MD, director of the Office of Vaccines Research and Review at FDA. Right now, a primary vaccine series for young children still requires two or three bivalent shots. Most other people receiving a vaccine for the first time only need one shot.

“Probably first and foremost [priority] is a uniform age cut-off for children transitioning from that multi-dose initial [series] to the single dose,” he said.

It’s possible that young children, older adults, and immunocompromised individuals will need more vaccine than the general population. It will be up to the CDC to make recommendations about who will get the updated shots and when.