mRNA-1010 Flu Vaccine Tops Standard-Dose Antibody Responses in Adults 50+

An investigational trivalent mRNA-based seasonal influenza vaccine, mRNA-1010, produced higher humoral immune responses against vaccine-matched influenza A and B strains than a licensed standard-dose (SD) influenza vaccine in adults aged ≥50 years. The results come from an immunogenicity analysis of the phase 3 FLUENT trial, published as an accepted manuscript in Open Forum Infectious Diseases.

FLUENT (NCT06602024) was a randomized, double-blind, active-controlled trial conducted during the 2024–2025 Northern Hemisphere influenza season. The authors noted that a single dose of mRNA-1010 previously showed a relative vaccine efficacy of 26.6% (95% CI, 16.7-35.4) against influenza illness compared with SD vaccine, with no safety concerns identified. This report describes Day 29 humoral immunogenicity.

The per-protocol immunogenicity subset included 2342 participants at North American sites. They were randomly assigned 1:1 to mRNA-1010 (37.5µg; 12.5µg per strain) or a licensed egg-based SD trivalent vaccine, and their median age was 64 years. At Day 29, hemagglutination inhibition (HAI) geometric mean ratios for mRNA-1010 vs the comparator were 1.82 (95% CI, 1.69-1.97) for A/H1N1, 1.59 (95% CI, 1.48-1.71) for A/H3N2, and 1.67 (95% CI, 1.57-1.78) for B/Victoria. Seroconversion rates were 55.0% vs 27.1% for A/H1N1, 60.8% vs 40.9% for A/H3N2, and 45.1% vs 19.7% for B/Victoria.

Investigators reported that responses were higher with mRNA-1010 across all prespecified subgroups. These included adults aged ≥65 years, participants with high-risk conditions and those who received an influenza vaccine the previous season. An exploratory microneutralization analysis in 500 participants measured neutralizing antibodies. In that analysis, Day 29 geometric mean ratios ranged from 1.37 to 2.81, and the lower bounds of the 95% CIs were above 1.0 for all strains.

The analyses were descriptive, with no formal hypothesis testing. The authors noted that some subgroups were small and that responses were measured only through Day 29 and against vaccine-matched strains. They also noted that the HAI assays used cell-derived viruses while the comparator was egg-derived, which could have contributed to the differences between groups. The investigators concluded that the findings support mRNA-1010 as an enhanced seasonal influenza vaccine candidate for adults aged ≥50 years.

Source: Leroux-Roels I, Malkin E, Chen H, et al. Humoral immunogenicity of mRNA-1010, an mRNA-based seasonal influenza vaccine, in adults ≥50 years. Open Forum Infect Dis. Published online October 13, 2026. doi:10.1093/ofid/ofag646