The Food and Drug Administration has told COVID-19 vaccine manufacturers to develop monovalent XBB.1.5 vaccines for the 2023-2024 fall and winter campaign, a major composition change intended to move U.S. vaccination away from the original-plus-Omicron bivalent formula and toward a single component better matched to currently circulating descendants of Omicron.

The agency announced the selection Friday, one day after its Vaccines and Related Biological Products Advisory Committee met to review epidemiology, vaccine effectiveness, variant surveillance and manufacturer data. In a June 16 update, FDA said it advised manufacturers seeking to update their vaccines that they should develop products with a monovalent XBB.1.5 composition. The agency said the decision incorporated advisory-committee input and the totality of available evidence, with the goal of making updated doses available in the fall.

Why the formula is changing again

COVID-19 vaccines have been operating in a moving biological target. The bivalent mRNA vaccines used during the 2022-2023 season combined the original SARS-CoV-2 strain with an Omicron BA.4/BA.5 component. By mid-2023, however, BA.4 and BA.5 were no longer dominant. FDA’s June 15 briefing document described an environment in which XBB descendants accounted for most circulating virus and the antigenic distance between those variants and earlier vaccine components had increased.

The agency’s framework also reflects a broader attempt to simplify COVID vaccination. FDA had already moved in April to make bivalent mRNA vaccines the basis of most U.S. dosing and to streamline schedules for many age groups. The June meeting focused not on whether vaccines should continue to be updated, but on which strain or strains should be used for the next campaign and whether a monovalent approach made more sense than preserving an ancestral-virus component.

CDC scientists presented a detailed variant assessment showing the rapid turnover among XBB sublineages. XBB.1.5 had been prominent, while newer descendants including XBB.1.16 and XBB.1.9 lineages were increasing. The practical challenge was to select a strain early enough for manufacturers to produce hundreds of millions of doses while choosing a component likely to remain antigenically relevant months later.

Effectiveness data support updating, not abandoning, vaccination

The committee also reviewed how the current bivalent products were performing. A CDC vaccine-effectiveness presentation showed that protection against infection and milder illness wanes and is affected by immune-evasive variants, while protection against severe outcomes remains more durable, particularly after recent vaccination. Those patterns help explain why regulators are seeking a closer antigenic match without assuming that an updated formula will eliminate breakthrough infections.

The decision is therefore less analogous to replacing a failed product than to adjusting a vaccine in response to viral evolution. SARS-CoV-2 continues to change, population immunity is now a mixture of vaccination and infection, and the public-health objective has increasingly emphasized preventing severe disease, hospitalization and death. A more closely matched strain could improve immune responses against viruses expected to circulate during the respiratory season, but the degree of additional real-world protection will not be known until updated vaccines are deployed.

Global coordination also matters. The World Health Organization’s technical advisory group presented its composition assessment to the committee after recommending that future formulations move away from inclusion of the original SARS-CoV-2 strain and use an XBB-descendant lineage. U.S. regulators are making their own decision, but greater alignment among major regulatory systems can simplify manufacturing and improve the chances that evidence generated for one market is informative elsewhere.

Manufacturers show they can pivot to XBB

Manufacturers used the meeting to show how quickly their platforms could be redirected. Pfizer presented clinical and preclinical data supporting updated formulations, including work on XBB-related candidates. Moderna’s presentation similarly reviewed variant-vaccine development and immunogenicity data. Novavax, which uses a protein-based platform rather than mRNA, also presented evidence supporting an updated XBB-targeted product.

The production timetable is one reason the strain decision cannot wait until the fall. Vaccine manufacture involves updating the antigen, producing and testing material, assembling regulatory submissions, conducting quality review and distributing doses. FDA said it anticipates timely filings from manufacturers so the agency can determine whether updated products meet standards for safety, effectiveness and quality before the campaign begins.

That means Friday’s XBB.1.5 selection is a manufacturing and regulatory direction, not yet an authorization for people to receive a new product. Each manufacturer must submit the necessary data, and FDA must take product-specific action. Recommendations about who should receive an updated dose and at what interval will also involve the Centers for Disease Control and Prevention and its Advisory Committee on Immunization Practices.

A narrower target for a broader immune landscape

The shift to monovalent XBB.1.5 is notable because it removes the original Wuhan-strain component that anchored the first generation of vaccines and remained part of the bivalent formula. FDA’s advisers examined whether keeping that older component could dilute immune responses to newer variants or offer useful breadth. The committee’s discussion favored moving toward an XBB-lineage target for the next season, reflecting the virus’s substantial antigenic movement since 2020.

The FDA meeting record makes clear that the decision rested on several different evidence streams rather than one trial: surveillance of which variants are circulating, antigenic characterization, existing vaccine effectiveness, immune-response data and the feasibility of producing updated formulations on schedule. None can predict perfectly what variant will dominate months from now.

That uncertainty is inherent in seasonal vaccine design. XBB.1.5 is not the only XBB descendant in circulation, and newer variants may gain ground before fall. Regulators are betting that the immune response generated by an XBB.1.5 antigen will provide useful cross-protection within the broader XBB family while allowing manufacturers to deliver doses on time.

The policy also marks another step toward treating COVID-19 vaccination as a periodically updated program rather than a fixed primary series followed indefinitely by boosters against older strains. FDA has discussed a more predictable strain-selection process similar in concept, though not identical, to influenza vaccine updates. Whether SARS-CoV-2 settles into a cadence that permits such regularity remains uncertain.

For the coming season, however, the direction is now concrete. Manufacturers have been told to build toward a monovalent XBB.1.5 vaccine, regulators will review the resulting submissions, and public-health officials will later decide how the updated products should be used. The science will continue to move, but the manufacturing clock for fall 2023 has already started.