Influenza remains a major global health challenge as continual antigenic drift can limit the breadth and durability of vaccine-induced antibody responses, requiring frequent vaccine updates. Researchers are therefore seeking strategies to generate broader, longer-lasting protection. A key focus is the germinal-center (GC), where B cells undergo selection and somatic hypermutation to produce diverse, high-affinity antibodies and long-lived memory B cells.
Researchers from Korea University College of Medicine, Republic of Korea, led by Associate Professor Jiwon Lee in the Department of Convergence Medicine and the Vaccine Innovation Center, investigated whether an mRNA-based influenza vaccine could stimulate stronger and more persistent GC responses than a conventional split-virion vaccine, potentially broadening antibody recognition. The study was conducted in collaboration with Professor Ali Ellebedy and his group at Washington University in St. Louis, USA. The study evaluated the investigational quadrivalent mRNA-1010 vaccine against the licensed Fluarix vaccine and was published in Nature Immunology on June 15, 2026.
The study followed 75 healthy adults aged 20–50 years across two influenza seasons, with 38 receiving mRNA-1010 and 37 receiving Fluarix. Blood samples were collected through 26 weeks, while a subset underwent ultrasound-guided fine-needle aspiration of draining axillary lymph nodes to assess germinal-center responses. Researchers combined flow cytometry, ELISpot, single-cell RNA sequencing and B-cell receptor sequencing, serum IgG proteomics, and antibody binding and neutralization assays to comprehensively profile immune responses.
Dr. Lee explains, "We found that the mRNA vaccine elicited a substantially more diverse and broader serum antibody repertoire than Fluarix." Most notably, influenza-specific GC responses persisted for up to 26 weeks in 5 of 13 mRNA-1010 recipients, while persistent GCs were not detected among Fluarix recipients. The vaccine also increased the diversity of the serum IgG repertoire and promoted diversification of pre-existing B-cell lineages through somatic hypermutation. These changes were associated with broader antibody binding across antigenically diverse influenza strains and significantly greater increases in neutralization titers against 11 of 13 A/H1N1 viruses tested. Dr. Lee adds, "The mRNA platform does not simply produce more antibodies, it produces a more diversified antibody response, which leads to greater binding and neutralizing breadth."
A key strength of the study was Ig-Seq, a mass-spectrometry-based technology that identifies individual antibody clonotypes circulating in the blood after vaccination. Dr. Lee notes, "Conventional vaccine studies typically measure the bulk binding or neutralization titers, but Ig-Seq allows us to resolve that response down to individual antibody clonotypes." Together with B-cell sequencing, this molecular-level approach revealed not only the magnitude of the antibody response, but also which antibody lineages emerged, expanded, and diversified after vaccination. The authors identify Ig-Seq as a key strength of the study because it provides molecular-level information that conventional bulk antibody measurements cannot capture.
The study highlights the potential of mRNA technology to generate broader, more durable influenza immunity by sustaining GC activity and supporting continued B-cell evolution. Further studies are needed to determine whether these responses translate into multi-season protection or longer vaccination intervals. Future research should also investigate whether these benefits are maintained in older adults and immunocompromised populations, whose immune responses may differ from those of healthy younger adults.
Ultimately, persistent GC responses and molecular tools such as Ig-Seq could help guide the development of influenza vaccines designed to generate broader antibody responses against an evolving virus.
Reference
Title of original paper: mRNA-based influenza vaccine expands the B cell response breadth in humans
Journal: Nature Immunology
DOI: https://doi.org/10.1038/s41590-026-02569-5
About Korea University College of Medicine
Korea University College of Medicine is the medical school of Korea University. It is located in Seoul, South Korea. As one of the oldest medical schools in South Korea, it has been historically regarded as one of the country's top medical schools. The school was founded as Chosun Women's Medical Training Institute in 1928 by Rosetta Sherwood Hall. The institute was subsequently renamed several times and ultimately merged with Korea University to become Korea University College of Medicine. So far, the school has produced over 7,000 graduates, most of whom are working as prominent physicians and public health advocates worldwide. The Vaccine Innovation Center, Korea University College of Medicine, is dedicated to advancing vaccine research and development and serves as an important hub for vaccine-related research at the institution.
Website: https://medicine.korea.ac.kr/en/index.do
About author
Dr. Jiwon Lee is an Associate Professor in the Department of Convergence Medicine and the Vaccine Innovation Center at Korea University College of Medicine. He received his BA in Molecular and Cellular Biology from the University of California, Berkeley, in 2009, and his PhD in Chemical Engineering from the University of Texas at Austin in 2016. The Lee group develops high-resolution, multi-omics technologies that decode antibody responses at molecular resolution, combining repertoire sequencing with mass-spectrometry-based proteomics to map immune system responds to infection and vaccination. These insights guide the design of personalized therapeutics and vaccines. Before moving to Korea University, Dr. Lee held the Ralph and Marjorie Crump Professorship at Dartmouth College Thayer School of Engineering.
