Influenza Strain Partially Dodges Existing Immunity and Current Vaccine, BIDMC-Led Study Finds

Vaccine Still Boosts Antibody Protection Against “Subclade K”

BOSTON — This year’s dominant flu strain has an unusual number of mutations, allowing it to partially escape existing immunity, investigators at Beth Israel Deaconess Medical Center (BIDMC) report. In a research letter published in JAMA, the team describes H3N2 “subclade K” and shows how it is less recognized by the immune system.

Influenza viruses evolve every year and can look different to the immune system, weakening the protection offered by prior immunity. This season, surveillance reports show that H3N2 strains account for more than 88 percent of all influenza detections, with H1N1 circulating at lower levels.

The study shows that while this year’s flu vaccine still boosts protection against the viral infection, the antibody response against subclade K — the dominant circulating H3N2 virus this year — is noticeably lower than the response to prior influenza strains, including H1N1 and other H3N2 strains. This finding points to a mismatch driven by viral evolution known as influenza drift.

“The rapid expansion of H3N2 subclade K is a major public health concern because both baseline and vaccine-induced immunity to this variant is lower than expected,” said corresponding author Dan H. Barouch, MD, PhD.

Barouch and colleagues compared the virus’s hemagglutinin — the main surface protein antibodies recognize — to the H3N2 protein in this season’s vaccine. They found 11 changes in that protein, including eight where antibodies usually latch on — helping explain why subclade K is able to evade the immune system.

The researchers then measured antibody responses in 46 healthy adults who received the 2025 trivalent inactivated influenza vaccine in Boston. Blood samples collected before vaccination and three weeks later were tested against five influenza strains — two subclade K viruses from 2025 and three earlier H1N1 and H3N2 strains.

Participants mounted strong antibody responses to the non‑K strains but weaker responses to subclade K. Across the 46 participants, people started with lower antibody levels against subclade K, and after vaccination they produced smaller increases than against other strains. Following vaccination, participants had three – to – eight fold lower neutralizing antibodies to the K strains compared with the non-K strains; another standard lab test (hemagglutination‑inhibition, or HAI) showed the same pattern.

“The vaccine still provides meaningful benefit,” noted first author Liping Wang, PhD. “However, the subclade K looks different enough from the strains the vaccine was designed to match that the boost in antibodies is more modest.”

Co-authors included Samuel J. Nangle, BS; Alejandra Waller‑Pulido, BS; Katherine McMahan, MS; Juliana Pereira, BS; Jayeshbhai Chaudhari, PhD; Leland O. Barrett, MS; Ritobhas Bhowmik, BA; Ai‑ris Y. Collier, MD; Dan H. Barouch, MD, PhD (Beth Israel Deaconess Medical Center/Harvard Medical School); Keith Ferrugia, MS; Reima Ramsamooj, MS; Emilia Mia Sordillo, MD, PhD; Viviana Simon, MD, PhD; Harm van Bakel, PhD (Icahn School of Medicine at Mount Sinai); Heba Mostafa, MD, PhD (Johns Hopkins School of Medicine); Andrew Pekosz, PhD (Johns Hopkins Bloomberg School of Public Health)

This work was supported by Massachusetts Consortium for Pathogen Readiness; philanthropic sources; NIH contracts 75N93021C000045 and 75N93021C00014. Funders had no role in study design, data collection, analysis, or publication decisions.

The authors report no conflicts of interest.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a leading academic medical center, where extraordinary care is supported by high-quality education and research. BIDMC is a teaching affiliate of Harvard Medical School, and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox.

Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.