On Thursday, the US Food and Drug Administration advised vaccine manufacturers to improve upon COVID-19 booster shots for this fall. The boosters will target both the original strain of the pandemic coronavirus and the two new Omicron subvariants—BA.4 and BA.5—which this week became the dominant versions of the virus circulating in the United States.
The FDA’s announcement comes two days after its independent expert advisors voted overwhelmingly in favor of updating the booster to include the Omicron ingredient. The vote was 19 in favor, two against—usually in favor of including an Omicron component. But, in their afternoon-long discussion, experts offered opinions that led to the FDA’s more specific guidance.
Notably, most of the committee expressed support for combination shots—aka divalent boosters—that would target both the original virus and Omicron’s version. Previously, there was widespread support to specifically target the omicron subvariants BA.4 and BA.5, rather than BA.1, which is no longer in vogue.
The BA.4 and BA.5 subvariants share a similarly mutated spike protein, which is important for infection and the targeting of COVID-19 vaccines. This similarity is the reason why the two often coexist, despite having different mutations elsewhere in their genomes. This week, BA.4 and BA.5 combined dominated the US, accounting for an estimated 52 percent of infections, according to the latest Centers for Disease Control and Prevention data. BA.5 is ahead, accounting for 36.6 percent, with BA.4 at 15.7 percent.
The pairings are quite different from previous versions of omron; They have a transmission advantage compared to the other subtypes and are also better able to avoid vaccine- and infection-based immunity. For these reasons, FDA experts felt that the next generation of boosters should target BA.4/5 and not the previous Omicron subvariants.
But this is somewhat of a gamble and time constraints. So far, leading vaccine makers Moderna and Pfizer-BioNtech have focused on updated vaccines that target the original Omicron variant, BA.1. Most of the data available on next-generation boosters includes BA.1, either in divalent formulas or alone. There are no clinical data yet on the efficacy of BA.4/5 vaccines.
But, if the FDA waits long enough to recommend an improvement, the dose will not be ready for the fall and winter. And it matters to the FDA, which sees the fall as primetime for a new infection surge. At that point, protection from current vaccine doses will be reduced and cold weather will move people indoors, where the risk of transmission is highest. Even as of today, June 30, with the FDA recommendation coming in, there will be pressure on vaccine manufacturers to roll out doses in October or early November.
This means that manufacturing will begin while clinical data on Ba.4/5 vaccines is still being collected and reviewed. In a statement on Thursday, the FDA’s top vaccine regulator Peter Marks 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 with modified vaccines containing the Omicron ba.1 component and we have advised them to submit these data to us prior to any potential authorization of a modified vaccine containing Omicron ba. Submit to FDA for evaluation. 4/5 components. Manufacturers will also be asked to start clinical trials with modified vaccines containing the Omicron BA.4/5 component, as these data will be of use as the pandemic further develops.
promptness and alertness
In a tweet thursdayPfizer CEO Albert Bourla said the company and its partner, BioNTech, are following the FDA’s guidance “to develop a bivalent Omicron ba.4/ba.5 subvariant vaccine booster, subject to regulatory authorization, in people’s health.” To help protect, as we enter the next chapter of the #COVID19 pandemic.” Borla said the mRNA-based vaccine platform allows for relatively rapid adjustments and the company is “ready to implement this process immediately.”
Still, some experts are wary of the FDA’s approach, including pediatrician Paul Offitt, director of the Center for Vaccine Education at Children’s Hospital of Philadelphia, and a member of the FDA’s expert advisory panel—one of two members who voted. against Updating a booster dose with an Omicron component.
In an opinion published Wednesday in State News, Offit and John Moore, a microbiology and immunology professor at Weill Cornell Medicine, argued that the FDA should wait for more data on the Omicron-focused booster before recommending it today. They argue that the BA.4/5 booster may not be much better than the current vaccines against BA.4/5 and may not provide as strong protection against whatever comes next.
Offit and Moore wrote Wednesday, “A multibillion-dollar decision to launch a vaccine that is based on a BA.1, BA.4, or BA.5 sequence that will affect more than 100 million people is unnecessary. There’s no need to be in a hurry.” Prior to the recommendation of the FDA. The FDA’s decision, he says, was “without fully weighing what the exact composition of the new vaccine should be, and assessing whether it offers a significant advantage over the current vaccine.”