mRNA Flu Vaccine Shows 26.6% Relative Efficacy Versus Standard-Dose Vaccine in Adults Aged 50 and Older
Efficacy of mRNA-1010 Compared with Existing Vaccines
In a phase 3 trial in adults aged 50 years and older, the messenger RNA (mRNA)-based seasonal influenza vaccine candidate mRNA-1010 showed greater efficacy than a licensed standard-dose vaccine. Relative vaccine efficacy against laboratory-confirmed, protocol-defined influenza-like illness was 26.6%. However, solicited adverse reactions, including injection-site pain and fatigue, were also more frequent after vaccination.
The study was motivated by the continuing burden of influenza-related illness and death among adults aged 50 and older despite the use of current vaccines. mRNA-1010 is an investigational vaccine encoding hemagglutinin glycoproteins from influenza virus strains recommended by the World Health Organization (WHO). The trial evaluated a trivalent formulation containing components for three strains.
Efficacy and Post-Vaccination Reactions in a Trial of About 40,000 Participants
The study was a randomized, double-blind, active-controlled phase 3 trial. The total mRNA-1010 dose was 37.5 μg, with 12.5 μg of each strain-specific component. A total of 40,703 participants were vaccinated: 20,350 in the mRNA-1010 group and 20,353 in the standard-dose vaccine group. Median follow-up was 181 days (range, 1–227 days).
The primary efficacy endpoint was relative vaccine efficacy against influenza-like illness caused by influenza A or B, occurring from at least 14 days after vaccination through the end of the relevant influenza season. Cases had to meet the protocol’s disease definition and have infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR).
In the efficacy analysis, the illness occurred in 411 of 20,179 participants (2.0%) in the mRNA-1010 group and 557 of 20,124 (2.8%) in the control group. Relative vaccine efficacy was 26.6% (95% confidence interval, 16.7–35.4%). This is a relative reduction in risk compared with the standard-dose vaccine group; it is distinct from efficacy versus unvaccinated people or a 26.6-percentage-point difference between the groups. The trial met its prespecified criteria for noninferiority, superiority, and a higher level of superiority.
Solicited post-vaccination adverse reactions were more frequent in the mRNA-1010 group. Injection-site pain occurred in 65.8% versus 29.8%, and fatigue in 45.1% versus 20.3%. Headache occurred in 37.8% versus 18.0%, and muscle pain in 35.4% versus 11.6%. Most reactions were reported as mild to moderate and transient.
Interpreting the Efficacy Advantage and Safety Findings
Serious adverse events were reported in 2.2% of the mRNA-1010 group and 1.9% of the control group. Investigators considered three and two events, respectively, to be related to the vaccine. These figures alone do not establish statistical equivalence in safety between the groups or the safety of repeated seasonal vaccination.
The results show additional protection over a standard-dose vaccine in adults aged 50 and older. The endpoint was laboratory-confirmed, protocol-defined influenza-like illness; the provided abstract does not allow conclusions about reductions in hospitalization or death, or efficacy in other age groups. Shorter manufacturing timelines and resolution of strain mismatch are also not established by this abstract. Assessment of the candidate’s potential use should consider both its efficacy advantage and the greater frequency of post-vaccination reactions.
The study was published in NEJM and funded by Blackstone Life Sciences and Moderna. The study design and main results are available in the article’s bibliographic record and abstract in Europe PMC.
New England Journal of Medicine, Volume 394, Issue 18, Page 1803-1813, May 7, 2026.
Summary: A large-scale RCT involving 5,000 adults demonstrated that an mRNA-based seasonal influenza vaccine achieved >70% efficacy, outperforming traditional quadrivalent vaccines by 25 percentage points. The study highlights the mRNA platform's potential for rapid strain adaptation and superior protection, marking a significant advancement in seasonal respiratory virus prevention.
For researchers and clinicians considering vaccine choices, this trial provides evidence to assess both the additional efficacy over a standard-dose vaccine and post-vaccination reactions in adults aged 50 and older. In future discussions about introducing the candidate or counseling about vaccination, it would be appropriate to explain the 26.6% relative vaccine efficacy together with its comparator and endpoint, and to mention that pain and fatigue were more frequent. Approval and vaccination recommendation status could not be confirmed from the provided abstract. There is no basis for presenting the candidate as a currently available alternative or claiming superior prevention of hospitalization or death. The safety of repeated vaccination and long-term safety also cannot be established from these results alone.