tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2026 Dec;22(1):2631804.
doi: 10.1080/21645515.2026.2631804. Epub 2026 Feb 17.
Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: Results from a phase 1, randomized, dose-escalation study
Isabel Leroux-Roels[SUP] 1 [/SUP], Ilse De Coster[SUP] 2 [/SUP], Alberto M Borobia[SUP] 3 [/SUP], Joanne M Langley[SUP] 4 [/SUP], Dolores Ochoa Mazarro[SUP] 5 [/SUP], Belén Ruiz-Antorán[SUP] 6 [/SUP], Stefano Berrè[SUP] 7 [/SUP], Sophie Germain[SUP] 8 [/SUP], Christine Knauer[SUP] 9 [/SUP], Sven D Koch[SUP] 10 [/SUP], Philipp Mann[SUP] 9 [/SUP], Doris Mesia Vela[SUP] 11 [/SUP], Leroy Jide Ovbude[SUP] 8 [/SUP], Iris Alessandra Pardo[SUP] 8 [/SUP], Barkha Srivastava[SUP] 10 [/SUP], Brian Moldt[SUP] 8 [/SUP], Marcus Nordgren[SUP] 8 [/SUP]
Affiliations
This first-in-human, randomized, controlled, phase 1 proof-of-principle study evaluated the safety, reactogenicity, and immunogenicity 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.Trial registration: NCT05446740.
Keywords: adverse events; cell-mediated immunity; hemagglutination inhibition titers; influenza; mRNA vaccine.
. 2026 Dec;22(1):2631804.
doi: 10.1080/21645515.2026.2631804. Epub 2026 Feb 17.
Safety and immunogenicity of an investigational mRNA-lipid nanoparticle-based monovalent influenza vaccine: Results from a phase 1, randomized, dose-escalation study
Isabel Leroux-Roels[SUP] 1 [/SUP], Ilse De Coster[SUP] 2 [/SUP], Alberto M Borobia[SUP] 3 [/SUP], Joanne M Langley[SUP] 4 [/SUP], Dolores Ochoa Mazarro[SUP] 5 [/SUP], Belén Ruiz-Antorán[SUP] 6 [/SUP], Stefano Berrè[SUP] 7 [/SUP], Sophie Germain[SUP] 8 [/SUP], Christine Knauer[SUP] 9 [/SUP], Sven D Koch[SUP] 10 [/SUP], Philipp Mann[SUP] 9 [/SUP], Doris Mesia Vela[SUP] 11 [/SUP], Leroy Jide Ovbude[SUP] 8 [/SUP], Iris Alessandra Pardo[SUP] 8 [/SUP], Barkha Srivastava[SUP] 10 [/SUP], Brian Moldt[SUP] 8 [/SUP], Marcus Nordgren[SUP] 8 [/SUP]
Affiliations
- PMID: 41701031
- DOI: 10.1080/21645515.2026.2631804
This first-in-human, randomized, controlled, phase 1 proof-of-principle study evaluated the safety, reactogenicity, and immunogenicity 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.Trial registration: NCT05446740.
Keywords: adverse events; cell-mediated immunity; hemagglutination inhibition titers; influenza; mRNA vaccine.