In this phase 1 study, an mRNA H1N1 influenza vaccine was generally safe and produced stronger immune responses than a licensed seasonal flu vaccine at doses above 1 microgram.
Evidence
This first-in-human randomized controlled dose-escalation trial compared FLUmHA with Flu D-QIV in younger adults aged 18-45 years and older adults aged 60-80 years and found dose-dependent rises in hemagglutination inhibition titers plus numerically higher Th1-skewed CD4+ T-cell responses.
Caveat
This was a monovalent phase 1 study, so it does not show real-world protection or broader performance of a multivalent influenza vaccine.
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.
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