Change to Covid vaccine formulation signals start of FDA pivot in immunization strategy

The FDA’s expert panel on vaccines voted Thursday to recommend that anyone who gets a primary Covid vaccine going forward will receive a bivalent shot instead of the original formula, signaling the start of the FDA's pivot to a longer-term immunization strategy.

It’s an important first step in a process that could result in millions of Americans getting an annual Covid booster, similar to the flu vaccine. Any such changes still require more discussion and decisions, but the FDA appears to be shifting from responding to the acute phase of the pandemic to a longer-term norm.

The agency’s Vaccine and Related Biological Products committee voted 21-0 to recommend replacing the originally authorized Covid-19 vaccine regime with the bivalent version of the vaccine. That version was reformulated last fall by Pfizer-BioNTech and Moderna to provide protection against the BA.4/BA.5 Omicron subvariants, which were widely circulating at the time and were capable of infecting those who had received the original vaccine series and booster.

Recent evidence suggests that the current bivalent provides protection against severe disease and death from the XBB.1 variant that is dominant in the U.S. right now.

“As we've turned the corner from a pandemic phase to an endemic phase,” said Ofer Levy, staff physician at Boston Children’s Hospital, professor at Harvard Medical School and a member of the FDA panel. “Today's vote marks a big practical win for the American people.”

According to the CDC, roughly 69 percent of adults living in the U.S. have completed their primary vaccination series. More than 80 percent have received at least one shot, but 20 percent remain completely unvaccinated. Only about 15 percent of Americans, or 50 million people, have received bivalent boosters so far.

Advisers stressed that this update would simplify immunizations going forward, which could result in more vaccinations.

“I think anything that results in better public communication, to get more of the unvaccinated vaccinated would be extremely valuable,” said Henry Bernstein, a professor of pediatrics at Hofstra University and a member of the advisory committee.

The recommendation still needs to be adopted by the FDA and the CDC before all vaccines are updated. Although the FDA doesn’t have to agree with its advisory committee, it often does.

“We think that simplification of the vaccination regimen would contribute to easier vaccine deployment and better communication and improved vaccine coverage,” said Jerry Weir, director of the division of viral products in the office of vaccines research and review at FDA.

The update would affect pediatric vaccines, including those for kids 5 and under. Vaccination rates among the youngest children are the lowest of all demographics; only 5.3 percent of children aged 2 to 4 and 3.5 percent of children six months to two years have completed a full vaccine series.

Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, said that for children under 2, the agency hopes to see more data on the bivalent vaccine. “The reassuring thing … is that the safety profile that we have seen with the bivalent boosters mirrors very well the original vaccine in this age range,” he said.

In addition to the panel’s recommendation, advisers focused their discussion Thursday on the best ways to move forward withCovid immunization strategies. 

One such strategy would be updating the vaccine annually based on the most widely-circulating variants and distributing it annually, similar to the flu shot. Given the fact that the vast majority of people in the U.S. have already been exposed to Covid-19, it’s possible that healthy adults and teens who have been previously vaccinated would need a single shot annually, while the youngest children, oldest adults or those with compromised immune systems would need two shots.

The advisers cautioned that directly mirroring flu vaccination schedules may not work for Covid, although they understood the desire to roll out an easily implementable endemic schedule. “We need to … make sure that we don’t just follow the dogma,” said Bruce Gellin, the chief of global public health strategy at the Rockefeller Foundation and member of the advisory committee.

They concluded more data would be needed before deciding on a concrete vaccination strategy moving forward. “In order to answer this question of how often, along with the immunogenicity and efficacy data, [we need] safety data,” said Hayley Gans, a professor of pediatrics at Stanford University Medical Center.

Still, the FDA stressed its desire to streamline the vaccination process to encourage those who are unvaccinated to get a vaccine. “We heard loud and clear that we need to use a data-driven approach to get to the simplest possible scheme that we can for vaccination,” said Marks. “It should be as simple as possible, but not over-simplified, a little bit like they say about Mozart's music.”

Advisers also weighed how manufacturers could harmonize any updates to Covid-19 shots to be based on the same variant. Currently, only the Pfizer-BioNTech and Moderna shots have been updated to induce immunity against BA.4 and BA.5 Omicron subvariants. Data suggests that these shots also produce immunity against the XBB.1 strain of the virus, which is currently the most commonly circulating virus. Novavax’s vaccine, which has been authorized as a primary series and booster for adults, has not yet been updated.

“We think we’re an important tool for boosting, and [for] this upcoming season,” said Filip Dubovsky, Novavax’s executive vice president and chief medical officer. Dubovsky said that the company would be looking for the agency’s recommendation on variant selection for future shots.

Novavax presented data that showed its primary vaccine provided ample protection against the BA.4/5 variants, unlike the mRNA shots that required earlier updating. But, he noted, that immunity waned against variants like XBB.1, suggesting it was time for an update.

“MRNA has been fantastic,” said Pamela McInnes, the retired deputy director of the National Center for Advancing Translational Sciences at the National Institutes of Health and voting member. “But it may not give us the breadth of coverage, which is really what I think our problem is right now.”

Some advisers felt it was still too early to say whether managing Covid-19 moving forward would require annual visits. “We may or may not need annual vaccination,” said Cody Meissner, a pediatrician at Tufts Children’s Hospital. “It’s just awfully early, it seems to me, in this process.”

“I don’t think we’re setting it in stone and we’ll see how it goes. We may need to adjust along the way. But overall, I think this is a good path,” said Gellin.