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The current predominant strain of COVID-19 should be a key consideration during the upcoming meeting of an FDA advisory committee tasked with making recommendations about the next COVID vaccine, agency staff said in a released Monday.

"Although JN.1 sublineages were predominant through spring 2024 in the U.S., the KP.2 subvariant has now become the predominant circulating strain," the authors noted. "Because the antigenic distance between JN.1 and JN.1-derived subvariants such as KP.2 subvariants is not far, it is possible that vaccines developed against JN.1 may adequately protect against KP.2. However, further SARS-CoV-2 evolution may lead to further divergence from JN.1, and consideration may need to be given to the selection of the subvariant that is currently predominant to assure the best possible match as the virus further evolves."

The document was released in advance of of the agency's Vaccines and Related Biological Products Advisory Committee. Following presentations and committee discussion, committee members will be asked to vote "Yes," "No," or "Abstain" on the question, "For the 2024-2025 formula of COVID-19 vaccines in the U.S., does the committee recommend a monovalent JN.1-lineage vaccine composition?" Presenters will include staff from the FDA and CDC; representatives of vaccine manufacturers Moderna, Pfizer, and Novavax; and a representative of the WHO's Technical Advisory Group on Coronavirus Vaccines (TAG-CO-VAC).

In the briefing document, the FDA staff gave a brief history of coronavirus vaccines, noting that two COVID vaccines -- Moderna's Spikevax and Pfizer's Comirnaty -- have been approved for COVID-19 prevention in persons 12 and older, while three other vaccines -- one from Moderna, one from Pfizer, and one from Novavax -- have emergency use authorizations for COVID prevention in various age groups. The document's authors emphasized that any recommendation for updating the vaccines' antigenic composition "must consider the time needed for manufacturers to implement and deliver" a new vaccine.

Since the introduction of the 2023-2024 updated vaccine, COVID-19 "has continued evolving into distinct sublineages by acquiring additional mutations," the briefing document said. "Although real-world effectiveness studies suggest that currently approved/authorized COVID-19 vaccines (2023-2024 formula) continue to provide protection against more currently circulating XBB sublineages, in prior years there appears to have been an inverse relationship between the time since vaccination and vaccine effectiveness, such that COVID-19 vaccine effectiveness against SARS-CoV-2 sublineages appears to wane over time and that better matching of the vaccine to circulating strains is associated with improved neutralizing antibody titers."

"Consistent with this observation, a decrease in effectiveness of COVID-19 vaccines (2023-2024 Formula) against COVID-19 caused by JN.1 lineage viruses has been reported," the authors wrote. "Available data suggest that updating the current formula of COVID-19 vaccines to more closely match currently circulating JN.1 lineage viruses is warranted for the anticipated 2024-2025 respiratory virus season in the U.S."

The authors also cautioned that the virus continues to evolve. "SARS-CoV-2 evolution continues to be complex and remains unpredictable," they wrote. "There is no indication that SARS-CoV-2 evolution is slowing, though immunity appears to be mitigating severe clinical outcomes, particularly in younger populations. Intrinsic viral factors, including mutation rate and recombination potential, generate possibilities for increased transmissibility and adaptation to the host. At the same time, host immune responses and other factors contribute to selection of variants."

The briefing document also discusses recommendations made by the WHO advisory group. In an April 26 statement, the group recommended that "As the virus is expected to continue to evolve from JN.1, the TAG-CO-VAC advises the use of a monovalent JN.1 lineage as the antigen in future formulations of COVID-19 vaccines." However, the briefing document added, "The TAG-CO-VAC recommendation for a monovalent JN.1 lineage vaccine was made at a time when JN.1 was almost completely dominant and before JN.1 lineage-derived virus variants with FLiRT mutations, such as KP.2, became dominant in the U.S. This change in epidemiology warrants consideration."

FDA officials will take the advisory panel's recommendation into account when it considers which updated vaccines to approve and/or authorize. The agency does not have to follow its advisory panels' recommendations, but often does. The CDC's Advisory Committee on Immunization Practices (ACIP) will also weigh in with recommendations on use of the vaccines.

The FDA advisory committee meeting comes at a time when vaccine uptake is low. As of May 11 -- the latest date for which figures were available -- 22.5% of adults reported receiving an updated COVID vaccine since mid-September 2023, and 14.4% of children ages 6 months to 17 years were reportedly up to date on their COVID shots, .

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