Novel mRNA-based vaccine prevents flu infection in adults

The novel mRNA-based influenza vaccine mRNA-1010 has demonstrated superior efficacy over its standard-dose (SD) comparator in preventing RT-PCR–confirmed protocol-defined influenza disease in adults aged 50 years and above, reports a study presented at IDWeek 2025.

Furthermore, its relative vaccine efficacy (rVE) is consistent across vaccine-included strains, such as influenza B, and persists throughout the duration of the influenza season.

“mRNA-1010 showed higher efficacy across age groups, influenza strains, participant subgroups, including [those] at high risk of severe influenza, compared with SD vaccines,” said lead researcher Dr Eleanor Wilson, Moderna, Cambridge, Massachusetts, US.

Moreover, “mRNA-1010 also prevented more severe, medically attended influenza," she added.

Wilson and her team conducted a phase III, randomized, double-blind, active-controlled study in 40,703 adults (median age 64 years, 56.9 percent female, 82.6 percent White, 13.2 percent Black, and 10.4 percent Hispanic/Latino) in the 2024-2025 influenza season from 11 countries and 301 sites throughout the Northern Hemisphere.

Of the participants, 20,350 were randomized to a single dose of trivalent mRNA 1010 37.5 µg (12.5 µg hemagglutinin mRNA per strain) and 20,353 to an SD comparator (Fluarix 45 µg or Fluarix Tetra, Influsplit Tetra, or Alpharix Tetra 60 µg).

A stratified Cox proportional hazards model, with the study vaccination group as a fixed effect, was used to estimate the rVE and confidence intervals (CIs), adjusting for the randomization stratification factors (age [50–64, 65+ years] and previous influenza season vaccination status).

“The primary efficacy endpoint was rVE in prevention of the first episode of RT-PCR–confirmed protocol-defined influenza-like illness (ILI) caused by influenza A or B strains beginning ≥14 days after study vaccination through end of the influenza season,” Wilson said.

Over a median follow-up of 181 days, mRNA-1010 exhibited an rVE of 26.6 percent (95 percent CI, 16.7–35.4) against RT-PCR–confirmed protocol-defined ILI relative to SD comparator, which met the prespecified superiority criteria (lower bound of the 95 percent CI >9.1 percent; 1-sided p=0.0005). [IDWeek 2025, abstract 229]

Compared with SD influenza vaccines, mRNA-1010 demonstrated robust immune responses across influenza A and B strains.

“Similar to other licensed influenza vaccines, day 29 HAI titers elicited by mRNA-1010 act as surrogate endpoints reasonably likely to predict clinical benefit,” Wilson said.

Safety profile

In terms of safety, solicited adverse reactions within 7 days of vaccination occurred more frequently in the mRNA-1010 than the SD comparator group. However, most reactions were mild or moderate in severity, transient, and self-limiting. No safety concerns were identified.

The most common systemic reactions in the mRNA-1010 and SD comparator arms were fatigue (45 percent vs 20 percent) and headache (38 percent vs 18 percent), followed by myalgia (35 percent vs 12 percent), arthralgia (28 percent vs 11 percent), chills (23 percent vs 4 percent), nausea/vomiting (9 percent vs 3 percent), and fever (6 percent vs 1 percent).

“Reactogenicity was higher with mRNA-1010,” Wilson said. “However, most solicited adverse reactions were grades 1 or 2 and transient.”