Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: Results from a phase 1, randomized, dose-escalation study

Feb 17, 2026Human vaccines & immunotherapeutics

Safety and immune response of a new mRNA flu vaccine tested at different doses in a first human trial

AI simplified

mRNA Technology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Reporting rates for solicited adverse events following the FLUmHA vaccine ranged from 62.5% to 100% in younger adults across different dose levels.

Younger adults experienced higher rates of solicited adverse events with increasing FLUmHA doses compared to those receiving the licensed Flu D-QIV vaccine.
Severe adverse events were reported in 0.0% to 20.8% of younger adults vaccinated with FLUmHA, compared to 2.9% in those receiving Flu D-QIV.
In older adults, the rate of unsolicited adverse events within 28 days was 43.8% for FLUmHA versus 50.0% for Flu D-QIV.
Hemagglutination inhibition titers increased significantly from pre-vaccination levels to day 22, with dose-dependent responses observed in both age groups.
FLUmHA induced a numerically higher hemagglutinin-specific CD4+ T-cell response than Flu D-QIV, suggesting a potentially stronger immune response.

AI simplified

This first-in-human, randomized, controlled, phase 1 proof-of-principle study evaluated the safety, , and of an investigational mRNA-based monovalent influenza vaccine encoding influenza A/H1N1 hemagglutinin (FLUmHA). Younger adults (YA) aged 18-45 y received one dose of FLUmHA at one of 10 dose levels (0.5-100 µg, n = 24/25 per group) or licensed Flu Dresden-quadrivalent seasonal influenza vaccine (Flu D-QIV, n = 35) on day (D)1. Older adults (OA) aged 60-80 y received FLUmHA (18 µg, n = 32) or Flu D-QIV (n = 16). Reporting rates for solicited adverse events (AEs) occurring within 7 d post-vaccination generally increased with increasing FLUmHA dose levels, and were 62.5%-100% (severe: 0.0%-20.8%) in YA across FLUmHA dose levels versus 88.6% (severe: 2.9%) in Flu D-QIV-vaccinated YA, and 62.5% (severe: 0.0%) (FLUmHA) versus 56.3% (severe: 0.0%) (Flu D-QIV) in OA. Unsolicited AEs within 28 d post-vaccination were reported by 50.0%-70.8% of YA across FLUmHA dose levels versus 68.6% of Flu D-QIV-vaccinated YA, and by 43.8% (FLUmHA) versus 50.0% (Flu D-QIV) of OA. No safety concerns were identified. A/H1N1 hemagglutination inhibition titers increased from pre-vaccination to D22, with adjusted geometric mean increases (GMIs) of 6.2-36.7 across YA and OA groups; the observed response was dose-dependent and higher in FLUmHA (for doses > 1 µg) versus Flu D-QIV recipients. Titers decreased but remained above pre-vaccination levels at D183 (GMI: 2.9-14.0). Additionally, FLUmHA elicited a numerically higher hemagglutinin-specific CD4+ T-cell response (predominantly Th1 profile) than Flu D-QIV, both in YA and OA. These results support the progression to clinical development of a multivalent mRNA Flu vaccine candidate.: NCT05446740. Trial registration

Key numbers

62.5%–100%

Solicited Adverse Events Rate

Reported in younger adults across FLUmHA dose levels.

6.2–36.7

Geometric Mean Increase in HI Titers

Measured from pre-vaccination to day 22 in younger adults.

Higher than Flu D-QIV

CD4+ T-cell Response

Observed in younger adults receiving FLUmHA.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Featured in

mRNA TechnologyIssue #25

First-ever mRNA flu vaccine shows up to 36.7x stronger immune response than traditional shot

↗

Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: Results from a phase 1, randomized, dose-escalation study

Abstract

Key numbers

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the mrna technology brief