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FDA calls for fall boosters against BA.4/5 as subvariants take over the US

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dr.  Peter Marks, director of the Center for Biologics Evaluation and Research within the Food and Drug Administration, testifies at a Senate Committee on Health, Education, Labor and Pensions hearing on the federal response to the coronavirus on Capitol Hill on March 18, 2021, in Washington, DC.

enlarge dr. Peter Marks, director of the Center for Biologics Evaluation and Research within the Food and Drug Administration, testifies at a Senate Committee on Health, Education, Labor and Pensions hearing on the federal response to the coronavirus on Capitol Hill on March 18, 2021, in Washington, DC.

On Thursday, the US Food and Drug Administration advised vaccine makers to reformulate COVID-19 booster shots for this fall. The boosters would target both the original strain of the pandemic coronavirus and two new ommicron subvariants — BA.4 and BA.5 — that became the dominant versions of the virus circulating in the United States this week.

The FDA’s announcement comes two days after the independent expert advisors voted overwhelmingly to update boosters with an ommicron component. The vote – 19 for, two against – was just for including an ommicron component in general. But in their afternoon-long discussion, experts gave opinions that led to the FDA’s more specific guidelines.

In particular, a large part of the committee expressed support for combination injections – also called bivalent boosters – that would target both the original virus and a version of ommicron. There was also broad support for targeting the omicron subvariants BA.4 and BA.5 specifically, rather than earlier subvariants, such as the former, BA.1, which is no longer in circulation.

BA.4 and BA.5 subvariants share an identical mutated spike protein, which is critical for infection and the target of COVID-19 vaccines. This similarity is why the two are often lumped together, despite having different mutations elsewhere in their genomes. This week, BA.4 and BA.5 collectively achieved dominance in the US, accounting for an estimated 52 percent of infections, according to the latest data from the Centers for Disease Control and Prevention. BA.5 leads the way, accounting for 36.6 percent, with BA.4 accounting for 15.7 percent.

The pair is significantly different from previous versions of ommicron; They have a transmission advantage over other subvariants and are even better at evading vaccine- and infection-based immunity. For these reasons, the FDA’s experts believed that the next generation of boosters should target BA.4/5 rather than bygone omicron sub-variants.

FDA’s move

But this is a bit of a gamble – and a time crisis. So far, leading vaccine makers Moderna and Pfizer-BioNTech have focused on updated vaccines targeting the original omicron variant, BA.1. The vast majority of available data on next-generation boosters relates to BA.1, either in bivalent formulations or alone. There are no clinical data on the efficacy of BA.4/5 vaccines yet.

But if the FDA waits longer to recommend a reformulation, the doses won’t be ready for fall and winter. And this is critical for the FDA, which considers the fall primetime for another wave of infection. At that point, protection from current vaccine doses will wane and cold weather will drive people indoors, where the risk of transmission is greatest. Even with the FDA recommendation coming today, June 30, vaccine makers will be under pressure to make doses available by October or early November.

That means production will start while clinical data on BA.4/5 vaccines are still being collected and reviewed. In a statement Thursday, Peter Marks, the FDA’s top vaccine regulator, assured Americans that “any COVID-19 vaccine authorized or approved by the FDA will meet our standards for safety and effectiveness.”

His statement continued:

Vaccine manufacturers have already reported data from clinical trials of modified vaccines containing an omicron BA.1 component and we have advised them to submit this data to the FDA for our review before any approval of a modified vaccine containing an omicron BA. 4/5 part. Manufacturers will also be asked to initiate clinical trials of modified vaccines containing an omicron BA.4/5 component as this data will come in handy as the pandemic continues to evolve.

Readiness and caution

In a tweet thursdayPfizer CEO Albert Bourla said the company and its partner, BioNTech, are following FDA guidelines to “develop a bivalent Omicron BA.4/BA.5 subvariant vaccine booster to help protect people depending on the regulatory approval as we move into the next chapter of the #COVID19 pandemic.” Bourla added that the mRNA-based vaccine platform allows for relatively rapid customization and that the company is “ready to implement this process immediately.”

Still, some experts are wary of the FDA’s approach, including pediatrician Paul Offit, the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and a member of the FDA’s expert advisor panel — one of two members voted against updating the booster dose with an ommicron component.

In an op-ed published Wednesday in Stat News, Offit and John Moore, a professor of microbiology and immunology at Weill Cornell Medicine, argued that the FDA should wait for more data on ommicron-targeted boosters before making the recommendation they are making today. did. They argue that a BA.4/5 booster will ultimately not be significantly better than current vaccines against BA.4/5 and may not offer strong protection against what comes next.

“There is no need to unnecessarily rush a multi-billion dollar decision to launch a vaccine based in whole or in part on the BA.1, BA.4 or BA.5 sequence that would affect more than 100 million people” , Offit and Moore wrote on Wednesday. , before the FDA’s recommendation. The FDA’s decision, they say, was made “without considering fully what the exact composition of the new vaccine should be, and without assessing whether it offers significant advantages over the current vaccine.”

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