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TOPLINE:

A single dose of an investigational mRNA-based vaccine called mRNA-1010 vaccine showed superior efficacy to a licensed standard-dose inactivated seasonal influenza vaccine in preventing influenza-like illness among adults aged 50 years or older, with a comparable safety profile. 

METHODOLOGY:

• This phase 3 randomized trial, conducted during the 2024-2025 Northern Hemisphere influenza season, investigated the efficacy of the mRNA-1010 vaccine — which encodes hemagglutinin glycoproteins from World Health Organization-recommended influenza strains — vs licensed standard‑dose seasonal influenza vaccines for preventing laboratory‑confirmed influenza‑like illness in adults aged 50 years or older.
• Overall, 40,703 vaccine recipients were assigned to receive a single intramuscular dose of mRNA-1010 (n = 20,350; 37.5 μg trivalent formulation; 12.5 μg per strain) or a licensed standard‑dose inactivated seasonal influenza vaccine (n = 20,353; preferably a trivalent formulation; a quadrivalent formulation was used when a trivalent formulation was unavailable).
• The primary endpoint was the relative vaccine efficacy of mRNA-1010 vs the standard‑dose comparator against the first episode of protocol‑defined influenza‑like illness caused by any influenza A or B strain and confirmed by using reverse transcriptase-polymerase chain reaction (RT‑PCR), assessed from 14 days after vaccination through the end of the influenza season.
• Protocol‑defined influenza‑like illness was an RT‑PCR-confirmed influenza infection along with at least one systemic symptom (fever characterized by body temperature > 37.2 °C, chills, feverishness, fatigue, headache, or myalgia) and at least one respiratory symptom (sore throat, cough, sputum production, wheeze, or difficulty breathing) occurring within 7 days before or after the positive test.
• Secondary endpoints were relative efficacy against RT‑PCR-confirmed, modified CDC defined influenza‑like illness (fever characterized by body temperature > 37.2 °C and cough or sore throat) and against protocol‑defined influenza‑like illness caused by strains antigenically matched to the vaccine. 

TAKEAWAY:

• RT-PCR-confirmed, protocol-defined influenza-like illness occurred in 411 of 20,179 recipients of mRNA-1010 (2.0%) vs 557 of 20,124 recipients of the standard-dose comparator vaccine (2.8%), corresponding to a relative vaccine efficacy of 26.6% (95% CI, 16.7-35.4) and meeting all prespecified criteria for noninferiority and superiority thresholds (P < .001 for all).
• The relative vaccine efficacy for RT-PCR-confirmed, modified CDC-defined influenza-like illness was 23.5% (95% CI, 9.0-35.8), meeting noninferiority and superiority criteria but not the higher superiority threshold.
• Adverse events were more frequently reported with mRNA-1010 than with the standard-dose comparator; the most commonly reported events were injection-site pain (65.8% vs 29.8%), fatigue (45.1% vs 20.3%), headache (37.8% vs 18.0%), and myalgia (35.4% vs 11.6%).
• Serious adverse events were reported in 2.2% of recipients of mRNA-1010 and 1.9% of recipients of the standard-dose comparator.

IN PRACTICE:

“These findings support the role of mRNA-1010 in improving influenza prevention,” the authors wrote. 

SOURCE:

The study was led by Isabel Leroux‑Roels, MD, Ghent University and Ghent University Hospital, Ghent, Belgium. It was published online on May 6, 2026, in The New England Journal of Medicine.

LIMITATIONS:

The number of cases was limited in some subgroups, including recipients aged 75 years or older and those considered vulnerable or frail, which may have resulted in wide CIs.

DISCLOSURES:

This study was supported by Blackstone Life Sciences and Moderna. Seven authors reported being employees of Moderna. Some authors reported receiving contract and institutional payments for conducting trials for various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.