tetano
Editor, Senior Moderator
Infect Dis Ther
. 2026 Oct 15.
doi: 10.1007/s40121-026-01463-9. Online ahead of print.
Ilse De Coster 1 , Jose F Cardona 2 , Murdo Ferguson 3 , Isabel Leroux-Roels 4 , Haylene Nell 5 , Stefano Berrè 6 , Sonia Schoonbroodt 6 , Clarisse Lorin 7 , Leroy Jide Ovbude 7 , Brian Moldt 8 ; FLU SV mRNA-002 study group
Collaborators, Affiliations Expand
Introduction: Hemagglutinin (HA) is the principal immunologic target of most licensed seasonal influenza vaccines. Targeting both HA and neuraminidase (NA) might improve vaccine effectiveness. This randomized phase 1/2 study evaluated an investigational mRNA-based quadrivalent seasonal influenza vaccine, encoding HA and NA of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata (FLUm4HA-4NA).
Methods: In phase 1, adults aged 18-50 years received either one of twelve mRNA vaccine formulations of varying HA-only or HA and NA mRNA doses, or a licensed quadrivalent seasonal influenza comparator. In phase 2, participants aged 18-64 years (younger adults) and 65-85 years (older adults) received FLUm4HA-4NA (three groups per age category, with different HA/NA mRNA doses) or age-appropriate licensed quadrivalent comparator. Primary endpoints were safety/reactogenicity, and hemagglutination inhibition [HI] and NA inhibition [NI] responses against the four seasonal strains at day 29. Cross-reactive HI/NI responses against drifted strains, virus neutralization, and HA-/NA-specific cell-mediated immunity were evaluated in phase 2 as tertiary objectives.
Results: A total of 293 participants (21-25 per group) were vaccinated in phase 1, 480 younger (108-137 per group) and 483 older adults (117-125 per group) in phase 2. Solicited events were more frequent with FLUm4HA-4NA than comparators and were mostly short-lived and mild or moderate. No deaths or vaccine-related serious adverse events were reported. Post-vaccination HI and neutralizing titers in the FLUm4HA-4NA groups were similar or higher for the A strains and lower for the B strains versus comparators. NI responses exceeded those of comparators for all four strains. HI and NI titers against evaluated drifted A strains were similar or higher after FLUm4HA-4NA than after comparator vaccination. HA-specific CD4+ and CD8+ T-cell responses were generally higher after FLUm4HA-4NA than comparator vaccination.
Conclusions: FLUm4HA-4NA showed an acceptable safety profile and humoral and cellular immunogenicity in the study population, supporting further development and formulation optimization to improve influenza B HI responses.
Trial registration: ClinicalTrials.gov: NCT05823974; euclinicaltrials.eu: 2022-502308-66-00.
Keywords: Adverse events; Cell-mediated immunity; Drifted strain; Hemagglutination inhibition assay; Hemagglutinin; Influenza; Neuraminidase; Neuraminidase inhibition assay; Next-generation influenza vaccine; mRNA vaccine.
. 2026 Oct 15.
doi: 10.1007/s40121-026-01463-9. Online ahead of print.
A Phase 1/2 Trial Evaluating the Safety and Immunogenicity of an mRNA-based Seasonal Influenza Vaccine Candidate Encoding Hemagglutinin and Neuraminidase
Ilse De Coster 1 , Jose F Cardona 2 , Murdo Ferguson 3 , Isabel Leroux-Roels 4 , Haylene Nell 5 , Stefano Berrè 6 , Sonia Schoonbroodt 6 , Clarisse Lorin 7 , Leroy Jide Ovbude 7 , Brian Moldt 8 ; FLU SV mRNA-002 study group
Collaborators, Affiliations Expand
- PMID: 42875683
- DOI: 10.1007/s40121-026-01463-9
Abstract
Introduction: Hemagglutinin (HA) is the principal immunologic target of most licensed seasonal influenza vaccines. Targeting both HA and neuraminidase (NA) might improve vaccine effectiveness. This randomized phase 1/2 study evaluated an investigational mRNA-based quadrivalent seasonal influenza vaccine, encoding HA and NA of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata (FLUm4HA-4NA).
Methods: In phase 1, adults aged 18-50 years received either one of twelve mRNA vaccine formulations of varying HA-only or HA and NA mRNA doses, or a licensed quadrivalent seasonal influenza comparator. In phase 2, participants aged 18-64 years (younger adults) and 65-85 years (older adults) received FLUm4HA-4NA (three groups per age category, with different HA/NA mRNA doses) or age-appropriate licensed quadrivalent comparator. Primary endpoints were safety/reactogenicity, and hemagglutination inhibition [HI] and NA inhibition [NI] responses against the four seasonal strains at day 29. Cross-reactive HI/NI responses against drifted strains, virus neutralization, and HA-/NA-specific cell-mediated immunity were evaluated in phase 2 as tertiary objectives.
Results: A total of 293 participants (21-25 per group) were vaccinated in phase 1, 480 younger (108-137 per group) and 483 older adults (117-125 per group) in phase 2. Solicited events were more frequent with FLUm4HA-4NA than comparators and were mostly short-lived and mild or moderate. No deaths or vaccine-related serious adverse events were reported. Post-vaccination HI and neutralizing titers in the FLUm4HA-4NA groups were similar or higher for the A strains and lower for the B strains versus comparators. NI responses exceeded those of comparators for all four strains. HI and NI titers against evaluated drifted A strains were similar or higher after FLUm4HA-4NA than after comparator vaccination. HA-specific CD4+ and CD8+ T-cell responses were generally higher after FLUm4HA-4NA than comparator vaccination.
Conclusions: FLUm4HA-4NA showed an acceptable safety profile and humoral and cellular immunogenicity in the study population, supporting further development and formulation optimization to improve influenza B HI responses.
Trial registration: ClinicalTrials.gov: NCT05823974; euclinicaltrials.eu: 2022-502308-66-00.
Keywords: Adverse events; Cell-mediated immunity; Drifted strain; Hemagglutination inhibition assay; Hemagglutinin; Influenza; Neuraminidase; Neuraminidase inhibition assay; Next-generation influenza vaccine; mRNA vaccine.