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

Recent evidence suggests that the current bivalent provides protection against severe disease and death from the XBB.1 variant that is predominant in the United States right now.

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

According to the CDC, approximately 69 percent of adults living in the United States have completed their primary vaccination series. More than 80 percent have received at least one injection, but 20 percent remain completely unvaccinated. Only about 1[ads1]5 percent of Americans, or 50 million people, have received bivalent boosters so far.

Advisers stressed that this update will simplify vaccinations 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 CDC before all vaccines are updated. Although the FDA does not have to agree with its advisory committee, it often does.

“We believe that simplifying the vaccination regimen will contribute to easier deployment of vaccines and better communication and improved vaccine coverage,” said Jerry Weir, director of the Division of Viral Products in the FDA’s Office of Vaccine Research and Review.

The update will affect pediatric vaccines, including vaccines for children 5 and under. The vaccination rate among the youngest children is the lowest of all demographics; only 5.3 percent of children ages 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 very well mirrors the original vaccine in this age group,” he said.

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

One such strategy would be to update the vaccine annually based on the most circulating variants and distribute it annually, similar to the flu shot. Given the fact that the vast majority of people in the United States have already been exposed to Covid-19, it is possible that healthy adults and teenagers who have previously been vaccinated will need a single shot annually, while the youngest children, older adults or those with weakened immune system will need two shots.

The advisers warned 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 we’re not just following dogma,” said Bruce Gellin, head of global public health strategy at the Rockefeller Foundation and a member of the advisory committee.

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

Still, the FDA emphasized its desire to streamline the vaccination process to encourage those who have not been vaccinated 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 we can for vaccination,” Marks said. “It should be as simple as possible, but not simplistic, a bit like they say about Mozart’s music.”

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

“We believe we are an important tool for increasing, and [for] this upcoming season,” said Filip Dubovsky, Novavax’s Executive Vice President and Chief Medical Officer. Dubovsky said the company would look to the agency’s recommendation on variant selection for future shots.

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

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

Some advisers believed it was still too early to say whether handling Covid-19 would require annual visits in the future. “We may or may not need annual vaccinations,” said Cody Meissner, a pediatrician at Tufts Children’s Hospital. “It seems very early, I think, in this process.”

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