Research Summary

mRNA-1010 Shows Superior Influenza Vaccine Efficacy in Adults ≥50 vs Standard Vaccines

Edited by:
Anthony Calabro, MA

Key Highlights

  • mRNA-1010 showed superior relative vaccine efficacy compared with standard-dose influenza vaccines in adults aged 50 years or older.
  • RT-PCR–confirmed, protocol-defined influenza-like illness occurred in 2.0% of mRNA-1010 recipients and 2.8% of comparator recipients.
  • Solicited adverse reactions were more frequent with mRNA-1010 but most were mild to moderate and transient.
  • Serious adverse events were infrequent and occurred at similar rates in the mRNA-1010 and comparator groups.

Vaccination with the investigational mRNA seasonal influenza vaccine mRNA-1010 showed superior efficacy compared with licensed standard-dose influenza vaccines for prevention of RT-PCR–confirmed, protocol-defined influenza-like illness in adults aged 50 years or older, according to a phase 3 trial published in The New England Journal of Medicine.

The Fluent trial evaluated mRNA-1010 during the 2024–2025 Northern Hemisphere influenza season. The vaccine encodes hemagglutinin antigens from World Health Organization (WHO)–recommended A/H1N1, A/H3N2, and B/Victoria influenza strains for cell- or recombinant-based vaccines.

Researchers conducted a phase 3, double-blind, randomized, active-controlled trial at 301 sites in 11 Northern Hemisphere countries. Adults aged 50 years or older in medically stable condition were randomly assigned in a 1:1 ratio to receive a single intramuscular dose of trivalent mRNA-1010, 37.5 μg, or a licensed standard-dose inactivated seasonal influenza vaccine.

The primary efficacy endpoint was relative vaccine efficacy against the first episode of RT-PCR–confirmed, protocol-defined influenza-like illness caused by influenza A or B, beginning at least 14 days after vaccination through the end of the influenza season. Active surveillance included twice-weekly e-diary prompts for respiratory symptoms, with nasopharyngeal swabs collected within 72 hours after symptom onset among participants meeting protocol-defined respiratory illness criteria.

Study Findings

A total of 40,703 participants received mRNA-1010 or the standard-dose comparator and were included in the safety analysis population. The per-protocol efficacy population included 20,179 mRNA-1010 recipients and 20,124 comparator recipients, with a median follow-up of 181 days.

RT-PCR–confirmed, protocol-defined influenza-like illness occurred in 411 mRNA-1010 recipients (2.0%) and 557 standard-dose comparator recipients (2.8%). This occurrence corresponded to a relative vaccine efficacy of 26.6% (95% CI, 16.7 to 35.4), meeting prespecified criteria for noninferiority, superiority, and higher-level superiority.

For the key secondary endpoint of RT-PCR–confirmed influenza-like illness, according to the modified CDC definition, relative vaccine efficacy was 23.5% (95% CI, 9.0 to 35.8), meeting noninferiority and superiority criteria but not the higher superiority threshold. No further hypothesis testing was conducted after that step in the hierarchical testing sequence.

In supportive and exploratory analyses, relative vaccine efficacy appeared generally consistent across influenza strains and subgroups. Relative vaccine efficacy was 29.6% for A/H1N1, 22.2% for A/H3N2, and 29.1% for B/Victoria. Among participants aged 65 years or older, relative vaccine efficacy was 27.4% (95% CI, 12.1-40.0).

Solicited adverse reactions occurred more frequently with mRNA-1010 than with the standard-dose comparator. Injection-site pain occurred in 65.8% vs 29.8%, fatigue in 45.1% vs 20.3%, headache in 37.8% vs 18.0%, and myalgia in 35.4% vs 11.6%, respectively. Most solicited adverse reactions were mild to moderate and transient. Serious adverse events were reported in 2.2% of mRNA-1010 recipients and 1.9% of standard-dose comparator recipients.

Clinical Implications

According to the study authors, the findings suggest that mRNA-1010 provided superior protection against RT-PCR–confirmed, protocol-defined influenza-like illness compared with licensed standard-dose influenza vaccines in adults aged 50 years or older. The authors also stated that the greater frequency of solicited adverse reactions with mRNA-1010 should be weighed against the magnitude of protection against influenza.

The authors noted several limitations, including evaluation across only 1 influenza season and limited case numbers in some subgroups, including participants aged 75 years or older and vulnerable or frail adults. The number of influenza B cases was also small, which contributed to wider confidence intervals for strain-specific estimates.

Expert Commentary

“Vaccination with mRNA-1010 was superior to a licensed standard-dose comparator in preventing influenza,” the researchers concluded. “Solicited adverse reactions were more common in the mRNA-1010 group, which suggests a need for balancing assessment of temporary vaccine-induced reactogenicity events with the magnitude of protection against influenza. Serious adverse events were infrequent and similar in the two groups. These findings support the role of mRNA-1010 in improving influenza prevention.”

Reference:
Leroux-Roels I, Huang G, Ferguson M, et al. Efficacy and safety of an mRNA seasonal influenza vaccine in adults. N Engl J Med. 2026;394(18):1803-1813. doi:10.1056/NEJMoa251649