The investigational mRNA-based influenza vaccine, mRNA-1010 (Moderna), provokes a broader immune response than conventional seasonal flu vaccines and exerts activity against multiple strains of influenza virus, according to findings of a study published in Nature Immunology.1
"We are seeing that the mRNA flu vaccine doesn't just boost the immune system's response to what it has already seen, it can help expand and diversify the antibody response, covering a broader range of flu stains," said the study principal investigator Ali Ellebedy, PhD, Department of Pathology and Immunology, WashU Medicine, St. Louis, MO, in a statement released on publication of the study.2
This first mRNA-based influenza vaccine candidate was recently deemed safe and efficacious for preventing influenza illness in adults 50 years and older in a unanimous vote by an FDA advisory committee, and FDA action on the application is anticipated by August.
The mRNA-based technology that hastened development of vaccines against COVID-19 and the reformulations for circulating strains could also be advantageous in countering seasonal influenza.In addition to the shortened time for reformulation, the technology obviates reliance on time-consuming egg-based production, with the associated risk of antigen introduction.
The investigational mRNA influenza vaccine also appears to evoke a greater germinal center (GC) response than traditional vaccination, with higher antibodies titers and frequencies of memory B cells (MBC).The broader immunologic response suggests that the technology could advance efforts to develop a universal influenza vaccination that better meets the annual challenge of predicting, and protecting against circulating strains.
"These findings reveal a key role for persistent GC responses in broadening the repertoire of vaccine-induced antibodies," report Ellebedy and colleagues.
In a 2017 interview with this reporter, Anthony Fauci, MD, then director of the National Institute of Allergy and Infectious Diseases (NIAID), discussed the threats of future infectious disease outbreaks, as well as the seasonal challenge of influenza, and the goal of developing a universal influenza vaccine.
"Influenza is always a threat—at the seasonal level and at the potential for a pandemic level," Fauci said. "For that reason, we need to get a vaccine that we can stockpile and have ready for an emergency, instead of chasing it when it occurs."
Broader Immune Response to Influenza Viruses
Ellebedy and colleagues characterized the immunologic response to mRNA-1010 in healthy adult recipients of a quadrivalent version during the 2022-2024 Northern Hemisphere influenza virus seasons. The investigational vaccine was administered to 38 participants, while 37 received a licensed, split-virion quadrivalent vaccine (Fluarix) formulated to the recommended virus strains.
The investigators performed flow cytometric analysis on samples from axillary lymph nodes on the same side as the deltoid muscle vaccine injection.They found that at 6 months after vaccination, only the group receiving the investigational vaccine evidenced glycoprotein hemagglutinin (HA)-specific GC responses (in 5 of 13 participants across the two seasons).
What You Need to Know
he investigational mRNA vaccine induced sustained germinal center activity, higher memory B-cell responses, and a more diverse antibody repertoire, suggesting it may provide protection against a wider range of influenza strains.
By expanding antibody diversity and enhancing immune recognition of antigenically distinct viruses, mRNA-1010 demonstrated characteristics that researchers believe are important for developing longer-lasting, broadly protective influenza vaccines.
The immunology findings follow a recent unanimous FDA advisory committee vote that mRNA-1010 is safe and effective for adults aged 50 years and older, with an FDA decision on the vaccine expected in August 2026.
Other responses unique to the mRNA vaccine included increases in IgG clonotypic array, which they describe as consistent with enhanced recruitment and selection of diverse MBC-derived lineages in the context of the sustained GC response. In a B cell clonal lineage analysis, they detected three IgG clonotypes from recipients of mRNA-1010 that were not found in any of those receiving Flurarix, "likely reflecting the rarity of such clonotypes".
"These data indicate that mRNA-1010 not only increases the number of serum clonotypes but also updates pre-existing IgG clonotypes by eliciting a broader spectrum of intraclonal variants that constitute a major fraction of the postvaccination serium IgG response," Ellebedy and colleagues report.
Although the differences detected in magnitude and composition of the antibody response between vaccines was not associated with significant differences between hemagglutination inhibition (HAI) titers against A/H1N1 and A/H3N2 in this cohort, the investigators suggest that the more diverse pool of low-frequency MBCs elicited by mRNA-1010 should enhance immunologic response targeting.
"As a vaccine that elicits both strong protection against antigenically drifting seasonal influenza virus strains and broad binding against divergent strains is recommended for developing a universal influenza virus vaccine, the results suggest that mRNA-based vaccines would greatly contribute to advancing this goal," Ellebedy and colleagues conclude.
References
1. Metz HC, Yu T-G, Dixit K, et al. mRNA-based influenza vaccine expands the B cell response breadth in humans. Nat Immunol. 2026, Published online June 15. https://doi.org/10.1038/s41590-026-02569-5. Accessed June 22, 2026.
