By Marie Rosenthal, MS

In a unanimous decision, the FDA’s Vaccines and Related Biological Products Advisory Committee recommended the JN.1 and/or a specific JN.1-lineage strain should be used in the 2025-2026 formula for updated COVID-19 vaccines. 

As SARS-CoV-2 circulates, it has been mutating with one strain after another becoming dominant. The delta strain became dominant in India in 2020, but by around May 2021, it was the dominant strain around the world. Delta was supplanted by omicron by the end of that year, and that pattern has repeated itself throughout the course of the pandemic. 

Since the initial COVID-19 vaccines were based on the original strain, which is no longer circulating, the vaccine is updated each year. The decision for which strain should be in the updated vaccines is based on variant and genomic surveillance done at the CDC and around the world, which closely monitor strains. 

In the winter of 2023-2024, there was a strain replacement of XBB.1.5-like viruses with JN.1-like viruses globally, according to Natalie J. Thornburg, PhD, the chief of the CDC’s Respiratory Viruses Laboratory Branch, Coronavirus and Other Respiratory Viruses Division, at the National Center for Immunization and Respiratory Diseases. 

“And then JN.1, it clearly gained some sort of growth advantage, and JN.1 emerged in December-January ’23-’24,” Dr. Thornburg explained. Since January 2025, all the viruses have been predominantly descendants of JN.1.     

A new lineage, BA.3.2, has been identified in South Africa, which could indicate a shift, she said. However, very few sequences have been detected outside of South Africa. And although it is difficult to predict which strain will be dominant by the fall, when the new updated vaccines will be available, experts expect JN.1 to still be dominant. 

“The SARS-CoV-2 JN.1 virus variant that emerged in late 2023/early 2024 replaced previous XBB-lineage viruses in a global sweep, and the overwhelming majority of viruses detected since that time have been derived from JN.1,” added Jerry Weir, PhD, the director of the Division of Viral Products, Office of Vaccines Research and Review, at the FDA’s Center for Biologics Evaluation and Research. 

Although most people think of respiratory diseases as being more prominent in the fall and winter, COVID-19 has continued to have a summer wave. In fact, “the 2024 summer COVID-19 wave was larger than the 2024-2025 winter wave,” Dr. Thornburg said, which prompted some panelists, particularly Hayley Gans, MD, a clinical professor of pediatrics and infectious diseases at Stanford Medicine Children’s Health, in California, to question whether the updated vaccines should be started in warmer weather instead of the fall. 

“You alluded to the summer wave being actually more prominent in the last wave at least,” Dr. Gans said. “We do see this bimodal wave, but we do see a predominance in the summertime, and I’m just wondering about your thoughts around the timing of when we get together and think about it [deciding the new strain components]. 

“We’re trying to slate it into an influenza or a respiratory viral season, which typically is in the wintertime, but maybe that’s not what should be our approach,” she said.

Dr. Thornburg said it might still take a few years to decide the best time to start administering the boosters. She said five years of watching the pattern of viral circulation “is probably enough to say it circulates all year-round,” Dr. Thornburg said. “It doesn’t disappear in the United States. It has a bimodal wave, but I don’t think it’s been circulating long enough to say the summer wave will always be bigger than the winter wave.”

She said that may take a decade or more to see the definite pattern, but it should be watched and discussed in future meetings. “But [in regard to] the timing of considering the vaccine formulation when to roll out boosters, I really think that is for groups like you to consider. And I think it should be still considered when that’s best [to do],” Dr. Thornburg replied.

There was also an update on the disease rates. Hospitalization rates have declined since the 2021-2022 season among all age groups but are still highest among the oldest and youngest Americans, Dr. Thornburg said.

COVID-19 remains the second-leading cause of hospitalizations due to respiratory viruses, with 250,000 to 410,000 hospitalizations reported between October 2024 and May 2025, according to Spyros Chalkias, MD, the senior director of clinical development, COVID-19 vaccines, at Moderna Inc. And while down, there were still between 30,000 and 50,000 COVID-related deaths among U.S. adults in that same period. 

Despite this, more than 73% of adults hospitalized in 2023-2024 had not received the updated vaccine. 

Because the Novovax vaccine, which just received FDA approval in May, is a protein-based vaccine, it is a technology that people are more familiar with; therefore, it remains an important choice, according to Robert Walker, MD, the senior vice president and chief medical officer at Novavax. Its tolerability and acceptability profile is good, he added. 

The approval was granted on pivotal phase 3 clinical data that showed the vaccine was safe and effective in preventing COVID-19. 

Moderna has been able to assess the safety of the vaccine through active and passive surveillance, and more than 900,000 people have received it over two seasons. More than 450,000 adults 18 years of age and older received the Moderna updated KP.2 vaccine, and it was 53% effective in preventing COVID-related hospitalizations.

Over the past five years, more than 1.8 billion doses have been distributed worldwide, and myocarditis and pericarditis remain very rare, Dr. Chalkias added. The rates have been decreasing with significantly lower rates since the 2022-2023 season. 

Moderna will continue to monitor vaccine safety and effectiveness, according to Jacqueline Miller, MD, the chief medical officer at Moderna.

Kayvon Modjarrad, MD, PhD, the executive director of Vaccine Research and Development at Pfizer, said that 5 billion doses of the Pfizer-BioNTech vaccine have been distributed globally since the vaccine was authorized in 2020, and there have been 22 clinical studies enrolling more than 70,000 participants from 6 months to more than 65 years of age. In addition, there have been 12 post-marketing studies evaluating safety in more than 60 million people, and studies on five continents continue to monitor real-world effectiveness. “The BNT162b2 vaccine maintains a highly favorable benefit–risk profile,” Dr. Modjarrad said. 

The vaccine manufacturers have continued to update candidate vaccines at risk to generate data about the updated composition, according to Dr. Weir. Because the vaccines must be developed and produced in large quantities,  the final choice of antigen could affect the availability of updated vaccines this fall. 

“The totality of available evidence indicates that a monovalent JN.1-lineage vaccine is warranted for COVID-19 vaccines to be used in the U.S., but the continued evolution and diversity of JN.1-lineage viruses complicates the specific strain selection decision,” he said.

Updating the vaccine will be a continuous process, Dr. Weir noted, and he repeated several times that the decision is a difficult one to make because it requires predicting how the virus will behave. “SARS-CoV-2 continues to evolve without a well-defined seasonality and in an unpredictable manner,” Dr. Weir admitted. 

“What I have learned to expect of COVID-19 is you want to stay on your toes and expect the unexpected,” Dr. Thornburg said.