In August 2026, the FDA approved the first mRNA seasonal flu vaccine, mFLUSIVA, made by Moderna. Phase 3 clinical trial data and immunogenicity research found that mRNA technology, specifically mRNA-1010, generated immune responses against vaccine-matched influenza strains in adults 50 and older.
The clinical evidence behind the new seasonal influenza vaccine — clinical efficacy, immune response, and safety and reactogenicity — can tell clinicians how the vaccine performed and prepare them for preventive care conversations with patients this fall.
The Phase 3 randomized, double-blind, active-controlled study evaluated the safety, reactogenicity, and immunogenicity of mRNA-1010 in 40,703 adults ages 50 and older during the 2024-2025 influenza season.
Participants were randomly assigned to receive either mRNA-1010, the investigational seasonal influenza vaccine, or a licensed standard-dose influenza vaccine comparator.
Including an active comparator in clinical trials allowed researchers to compare the new vaccine with an established seasonal influenza vaccine rather than with a placebo.
The primary efficacy endpoint of Phase 3 was laboratory-confirmed, protocol-defined influenza-like illness caused by influenza A or B. Participants were evaluated beginning 14 days after vaccination through the end of the influenza season, with follow-up extending to approximately 6 months after vaccination.
The findings apply specifically to the population studied, the influenza season, and outcomes evaluated in the trial.
The researchers found that protocol-defined influenza-like illness occurred in 2 percent of participants who received the mRNA-1010 versus 2.8 percent of those who received the standard-dose comparator. The reported relative vaccine efficacy (RVE) was 26.6 percent. In the study, RVE describes the relative reduction in the risk of the specified influenza-like illness outcome with mRNA-1010 compared with the standard-dose vaccine comparator.
Importantly, the 26.6 percent RVE doesn’t mean that 26.6 percent of people who received mRNA-1010 were protected from influenza. It represents the relative reduction in the risk of the study-defined influenza-like illness outcome compared with the standard-dose comparator.
Additionally, influenza vaccine efficacy can vary considerably from season to season depending on circulating strains and other factors.
Immunogenicity is a vaccine’s ability to generate an immune response. Antibody measurements are a critical tool for evaluating how well a vaccine stimulates immune production. The hemagglutination-inhibition (HI) test is a core measurement used in vaccine research. HI testing measures whether antibodies in a blood sample can prevent influenza viruses from agglutinating, or clumping, red blood cells.
The Phase 3 immunogenicity study reported findings on the safety, reactogenicity, and humoral immunogenicity of mRNA-1010 versus licensed standard-dose and high-dose quadrivalent influenza vaccine from the three-part Phase 3 clinical trial. The results showed that a single dose of mRNA-1010 generated HI antibody responses against vaccine-matched strains that met the study’s criteria for superiority compared with the licensed standard-dose and high-dose influenza vaccine comparators. Adverse reactions were more frequent in participants receiving mRNA-1010, but less frequent and less severe among adults aged ≥65 years than among younger adults.
Two key differences separate the Phase 3 efficacy clinical trial and the Phase 3 immunogenicity study. The efficacy trial evaluated how the vaccine performed against a defined clinical outcome, while the immunogenicity study evaluated the immune response generated by vaccination. Both findings provide different pieces of evidence about mRNA’s performance.
Distinguishing reactogenicity from serious adverse events (SAEs) can help clinicians understand the safety of the new mRNA influenza vaccine. Reactogenicity is the subset of reactions that occur soon after vaccination. It can include injection site reactions such as pain, redness, swelling, or induration, as well as systemic symptoms, including fever, myalgia, or headache. Reactogenicity is generally more expected during vaccine clinical trials.
Serious adverse events are medical events that meet specific regulatory criteria, which can include events that result in hospitalization, disability, a life-threatening condition, or death. An SAE occurring during a clinical trial is not necessarily caused by the vaccine.
In the Phase 3 trial, the most frequently reported reactions reported included injection-site pain, fatigue, headache, and myalgia. These reactions — which ranged from mild to moderate — occurred more frequently among mRNA-1010 recipients than among those who received the standard-dose comparator. Serious adverse events occurred in 2.2 percent of participants who received mRNA-1010 compared with 1.9 percent of those who received the standard-dose comparator. Five deaths occurred during the study period. Researchers assessed two SAEs related to mRNA-1010.
Researchers didn’t identify a new safety signal during the study period.
For clinicians, post-approval safety monitoring remains critical because very uncommon events may not be detectable in a trial of this size.
Knowing who was represented in clinical trials can help clinicians understand how confidently they can apply study findings to the patients they serve. Racial and ethnic representation in clinical trials can help researchers evaluate whether the findings are consistent across diverse populations, although race alone doesn’t determine vaccine response. Clinicians must consider whether study populations reflect the patients they serve.
With the latest mRNA vaccine approval, patients will likely have questions about this new vaccine technology. Culturally responsive communication can help clinicians address patients’ questions, concerns, and experiences with the healthcare system while supporting informed vaccination decisions. It helps to build trust and address specific community values and historical context that can directly improve vaccine acceptance and uptake.
The Phase 3 clinical trial provides important evidence about mRNA-1010, but it cannot answer every question that may arise once the vaccine is used more broadly.
Post-approval evidence will help complement randomized clinical trial data and provide additional information about mRNA’s effectiveness and safety in broader populations and across future influenza seasons.
The Phase 3 clinical trial data revealed a 26.6 percent RVE for mRNA-1010 compared with a standard-dose influenza vaccine against the trial-defined influenza-like illness endpoint. The immunogenicity study also found that the vaccine generated antibody responses against vaccine-matched influenza strains.
Local and systemic reactions were more frequently reported with mRNA-1010 than with the comparator, although most were mild to moderate and temporary.
Together, the studies provide important clinical evidence for the first FDA-approved mRNA seasonal influenza vaccine. Continued real-world and post-approval evidence will help clarify its effectiveness and safety across future influenza seasons.
By subscribing, you consent to receive emails from BlackDoctor.pro You may unsubscribe at any time. Privacy Policy & Terms of Service.
Are you a healthcare professional? Register with us today!
