An advisory committee for the Food and Drug Administration on Thursday voted unanimously (21 to 0) to recommend updating COVID-19 vaccines for the 2023-2024 period to be a monovalent formula targeting the latest omicron subvariant lineage of XBB. Such an update would apply to both primary series shots as well as boosters.

The monovalent update means that the next COVID-19 vaccines will only target one version of pandemic coronaviruses. This is a switch from the current formula, which is bivalent, targeting both the spike protein from the ancestral SARS-CoV-2 strain and the previous leading omicron subvariants BA.4/5 (which share a spike protein).

In Thursday's day-long meeting, advisers reviewed data suggesting that the current bivalent vaccine continues to protect from the most severe outcomes of COVID-19, but protection from infection and hospitalization wanes over time and wanes notably faster against the XBB variants. To date, only 17 percent of Americans have received a bivalent booster, meaning their protection is significantly weakened since their last dose of the original vaccine formula, which only targeted the ancestral strain.

For the update, the advisers examined data suggesting that a monovalent vaccine, rather than a bivalent, would have a better shot at protecting against the latest omicron subvariants and reduce the chances of skewing immune responses back to the ancestral strain, which no longer circulates. Since the last update to the bivalent shots, the virus has continuously evolved, coming up with new ways to try to evade immune responses built up from previous infections and vaccinations.

The FDA does not have to follow the advisory committee's recommendations, but it almost certainly will in this case. The agency set a seemingly firm position of treating COVID-19 much like flu, with annual or biannual reviews of strain matches and updated vaccine formulas rolled out in the fall—barring a catastrophic variant that requires urgent, off-schedule responses.

Seasons and strains

Some of the advisers on the committee—the Vaccines and Related Biological Products Advisory Committee (VRBPAC)—once again gently pushed back on this plan, noting that they were not yet convinced that SARS-CoV-2 would be seasonal or has already become seasonal. Others, however, seemed more comfortable with the assumption. Committee chair Arnold Monto, a professor emeritus of epidemiology at the University of Michigan, noted that garden-variety coronaviruses that cause common colds each year are "sharply seasonal." He said it was "premature" to suggest that SARS-CoV-2 would not fall into a seasonal pattern. Regardless of the long-term seasonality, the advisers all agreed that, at least for now, a vaccine formula update is in order.

There was a little ambiguity about which XBB subvariant to target the updated vaccines against. Currently, the globally spread XBB.1.5 is the predominant subvariant in the US, accounting for about 40 percent of cases in the US, according to data from the Centers for Disease Control and Prevention. But, XBB.1.16, which now accounts for 18 percent of cases, is gaining ground and could be dominant in the fall. The FDA also has its eyes on XBB.2.3, which is growing in proportion and appears to be gaining ground against XBB.1.16 in India.

Preliminary data suggests that vaccines targeting the main XBB lineages offer about the same protection, with XBB.1.5 possibly offering a slight edge. In discussions, the advisers did not express a strong opinion on the specific XBB descendent for the strain but generally supported using XBB.1.5. If chosen, this would put the US in line with recommendations from advisers for the World Health Organization, which in May also recommended that countries updating vaccines move to monovalent formulas targeting the XBB lineage, with the recommendation specifically highlighting XBB.1.5.

Peter Marks, the FDA's top vaccine regulator, noted at the end of the meeting that the agency will "make a decision quickly regarding the specific composition to recommend to manufacturers." In terms of what the decision will be, Marks chuckled while saying: "I don't think it will come as any surprise based on the discussion today." Once the FDA decides, vaccine makers (Moderna, Pfizer-BioNTech, and Novavax) will work with the agency on developing and producing at scale their updated formulas, which Marks anticipated could be available around September.