The US Food and Drug Administration has recommended that vaccine manufacturers update their COVID booster shots to target the new forms of the Omicron variant. U calling for changeThe FDA heeded the recommendations of its Vaccines and Related Biological Products Advisory Committee (VRBPAC), which voted 19 to 2 in favor of the Omicron-adapted boosters after a June 28 public meeting. The new boosters may be deployed this fall, but that will likely be too late to prevent the current surge in cases resulting from the Omicron BA.4 and BA.5 subvariants in the US and other countries.
Existing vaccines target the ancestral form of SARS-CoV-2, the virus that causes COVID, which first emerged in the city of Wuhan, China. But while these vaccines still broadly protect against severe disease, “their effectiveness appears to be waning over time,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said at a VRBPAC meeting in late June. Each new variant was consistently more infectious than its predecessor. And around the world, Omicron subvariants are contributing to an increase in infections and hospitalizations — the latter especially among the elderly.
Planned upgrades are currently limited to vaccine mRNA accelerators developed by Moderna and the Pfizer-BioNTech collaboration. Now, these companies are racing against time to test new products and create the millions of doses needed to supply the FDA’s planned fall booster campaign.
Scientific American spoke with experts from academia and industry about the prospects for transitioning to these shots.
How will the new boosters be different?
Vaccines against COVID to date have only targeted the inherited virus. In addition to this virus, the new accelerators will target the Omicron BA.4 and BA.5 subvariants, which accounted for about 70 percent of new U.S. COVID cases as of July 2, according to the FDA’s recommendation. In selecting these targets, VRBPAC Members felt it was prudent to match boosters to currently circulating strains, but without compromising the protection against severe disease afforded by vaccines targeting the inherited virus. “We strongly believed that current vaccines still work very well, and we didn’t want to lose that,” says Archana Chatterjee, dean of the Chicago Medical School and a VRBPAC member. But with new variants emerging every three to four months, Chatterjee adds, there’s no guarantee the BA.4 and BA.5 will still be dominant when the fall reinforcement campaign begins.
Can vaccines adapted to Omicron be used in people who have not yet been vaccinated?
In the current state, the answer is no. Arrows are intended to be used as accelerators only. Unvaccinated people will still be able to receive the main vaccine series based on the parent strain.
How well do Omicron adapted boosters work?
Published evidence so far is limited to what Pfizer-BioNTech and Moderna have disclosed in press releases — especially for the updated boosters targeting the first Omicron variant, called BA.1. According to preliminary data, the shots elicit levels of neutralizing antibodies — antibodies that help the body fight the virus — twice as high as those produced by the companies’ existing vaccines. However, these data tell only part of the story because “there is no clear cut-off as to what antibody levels correlate with protection from the disease,” says Ofer Levy, VRBPAC member and director of the Precision Vaccines Program at Boston Children’s Hospital. In addition, the extent to which the Omicron-adapted boosters may elicit additional protection from immune cells called T cells and B cells remains unknown. Both companies have begun testing divalent accelerators aimed at BA.4 and BA.5, but have yet to release any data.
How long do the new accelerators last?
It’s hard to say. As long as there are new options with Omicron, protection can be solid. But if the next big option comes out of the blue, as it did with Delta and the original Omicron, then long-term protection is more questionable. However, not all experts agree that Omicron-adapted accelerators are justified based on current data. Paul Offit, a pediatrician at the Children’s Hospital of Philadelphia, agrees with the need for a booster this fall aimed at high-risk groups. But he argues that as long as existing vaccinations protect against serious illness and hospitalization, they are serving that purpose. Offit was one of two VRBPAC members who voted against updating the footage. “We all agree that the ancestral component should be there,” he says. “But will adding the Omicron component significantly increase antibodies against the next subvariant? There is no evidence that this will happen.”
Will the new boosters be available for all age groups, including young children?
This remains unclear. In response to an email Scientific American, an FDA official wrote: “FDA expects that, based on data to be submitted by manufacturers, it will be able to authorize modified boosters for those populations deemed eligible to receive them.” However, the agency declined to elaborate further on the review process.
What is happening now?
Pfizer-BioNTech and Moderna say they may begin shipping the BA.4-BA.5 divalent booster in October. However, the companies also say they need more guidance from the FDA about the types of data they must submit for regulatory approval. The wild card is how much human clinical information the FDA will seek. Existing vaccines were approved based on large-scale clinical trials involving tens of thousands of people. Accelerators adapted to Omicron are produced using the same manufacturing platforms and materials. The companies hope that the products will be approved solely on the basis of preclinical data showing adequate levels of neutralizing antibodies. “We would have been able to set the October deadline as long as the FDA accepts preclinical data rather than clinical data, which has been standard for previous emergency use approvals,” says Moderna spokeswoman Elise Meyer. Everything else “will be a change in approach to regulation.”