Vaccine advisers to the Food and Drug Administration (FDA) today recommended switching the SARS-CoV-2 strain from the XBB.1.5 variant to JN.1 for fall vaccine formulations.
The recommendation marks the third remake for the COVID vaccine since 2022. The measure unanimously passed, 16 to 0. FDA officials, concerned about further evolution of JN.1, also asked the group to discuss the possibility of recommending an offshoot of JN.1, such as KP.2, that may more closely match currently circulating strains.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) was originally slated to meet on May 16 but postponed its discussion until today to allow time to gather more surveillance data and other information so that the group has the most up-to-date information.
Improvements over XBB.1.5 vaccine
JN.1 became the dominant strain in the United States at the end of 2023, but it continues to evolve. Offshoots such as KP.2 and KP.3—now overshadowing the parent virus—have an immune-evasive spike mutation combination that added more complexity to strain-selection considerations. Scientists have nicknamed the spike mutations FLiRT (F for L at position 456 and R for T at position 346).
The JN.1 FLiRT variants are partly responsible for case rises in some countries, with early US indicators showing a slight uptick from very low illness levels.
In late April, the World Health Organization vaccine advisory group recommended a switch to a monovalent (single-strain) vaccine that contains the JN.1 antigen.
At today's meeting, VRBPAC members heard from experts at the FDA, the Centers for Disease Control and Prevention (CDC), and vaccine manufacturers.
Ahead of the vote, Jerry Weir, PhD, who directs the viral products division in the FDA's vaccines research office, said nonclinical data from three vaccine manufacturers suggest that updated JN.1 lineage formulations prompt stronger neutralizing antibody responses against JN.1-descendant lineage viruses than the current monovalent XBB.1.5 vaccine. He also said serology data from people infected with JN.1 show improved antibody responses against JN.1 lineages, compared with sera from XBB-infected people, though neutralizing antibody responses appear to be reduced by recent mutations in many JN.1 lineage viruses.
Virus diversity complicates discussions
After the vote, FDA officials asked advisory group members to weigh in on whether to select a specific JN.1 lineage, such as KP.2
During earlier presentations, a representative from Novavax said the company is already working on a JN.1 vaccine and that a switch to a newer lineage may mean the company won't be able to produce vaccine in time for the US market. Protein-based vaccines have longer manufacturing timelines—about 6 months, which is similar to flu vaccines—than mRNA vaccines do.
Most VRBPAC members said they thought JN.1 vaccines would provide good protection, and they didn't want to shut out the Novavax option for people who are unable to receive an mRNA vaccine or would prefer getting a protein-based vaccines.
Several members also said they weren't keen on "chasing variants." Melinda Wharton, MD, MPH, associate director for vaccine policy at the CDC's National Center for Immunization and Respiratory Diseases, said variants emerging when the updated COVID vaccines are released in August and September may not be the same as the ones the committee is discussing today, but will probably be related to JN.1.
Peter Marks, MD, who directs the FDA's Center for Biologics Evaluation and Research, pressed the group on whether it fully considered recommending a strain such as KP.2 that more closely matches circulating viruses. He also raised the possibility of exploring ways to give vaccine manufacturers a little more leeway on strains to include.
Michael Nelson, MD, PhD, professor of medicine and chief of the asthma, allergy, and immunology division at the University of Virginia School of Medicine, said he'd prefer a polyvalent vaccine containing JN.1 and KP.2, but for simplicity and based on reassuring neutralization data, JN.1 seems like a natural and obvious choice.
The group didn't vote whether to recommend a more specific strain, but FDA officials will take their views, alongside the earlier vote, into consideration when making its final recommendation to vaccine.
