tetano
Editor, Senior Moderator
Infect Dis Ther
. 2026 Oct 15.
doi: 10.1007/s40121-026-01462-w. Online ahead of print.
Brian Moldt 1 , Rafael A Ubeda 2 , Alexander V Murray 3 , Giresse Tima 1 , Sophie Germain 1 , Clarisse Lorin 1 , Leroy Jide Ovbude 1 , Danaé Steinbrecher 4 , Marcus Nordgren 5 ; FLU SV mRNA-024 study group
Affiliations Expand
Introduction: Influenza vaccines targeting both hemagglutinin (HA) and neuraminidase (NA) might offer broader protection than current vaccines, which primarily target HA. This randomized phase 2 study evaluated the immunogenicity and safety of an investigational mRNA-based trivalent seasonal influenza vaccine encoding HA and NA from A/H1N1, A/H3N2, and B/Victoria (FLUm3HA-3NA).
Methods: Participants aged 18-64 years (younger adults) or 65-85 years (older adults) received one of several mRNA vaccine formulations-each containing different influenza A and B HA mRNA doses-or an age-appropriate licensed seasonal influenza vaccine as a comparator. Four formulations per age cohort were tested in part 1 of the study, and one formulation per age cohort in part 2. Day-29 hemagglutination inhibition (HI) and NA inhibition (NI) responses were assessed as primary and secondary endpoints, respectively, safety/reactogenicity as the secondary, and virus neutralization as the tertiary endpoint.
Results: A total of 250 younger and 260 older adults were vaccinated in part 1; 161 and 162, respectively, in part 2. All FLUm3HA-3NA formulations induced HI, NI, and neutralizing responses above baseline. In part 1, HI responses against A/H1N1 and A/H3N2 were similar or higher after FLUm3HA-3NA than after comparator vaccination in both age groups. For B/Victoria, HI responses were lower or similar versus comparator vaccination in younger adults and similar or higher in older adults. In part 2, HI responses were similar or higher with FLUm3HA-3NA versus comparators for A/H1N1 and A/H3N2, and lower for B/Victoria in both age groups. In both study parts and both age groups, NI titers were higher for all three strains with FLUm3HA-3NA versus comparators, and neutralizing titers were similar or higher for A/H1N1 and A/H3N2 and similar for B/Victoria. No safety concerns were identified.
Conclusions: FLUm3HA-3NA induced HI, NI, and neutralizing responses, with an acceptable safety profile. The results support further development, including optimization of the influenza B HI response.
Trial registration: ClinicalTrials.gov: NCT06431607.
Keywords: Adverse events; Hemagglutination inhibition assay; Hemagglutinin, influenza; Neuraminidase; Neuraminidase inhibition assay; Next-generation influenza vaccine; Virus neutralization; mRNA vaccine.
. 2026 Oct 15.
doi: 10.1007/s40121-026-01462-w. Online ahead of print.
A Phase 2 Trial Evaluating the Immunogenicity and Safety of an mRNA-Based Seasonal Influenza Vaccine Candidate Encoding Hemagglutinin and Neuraminidase
Brian Moldt 1 , Rafael A Ubeda 2 , Alexander V Murray 3 , Giresse Tima 1 , Sophie Germain 1 , Clarisse Lorin 1 , Leroy Jide Ovbude 1 , Danaé Steinbrecher 4 , Marcus Nordgren 5 ; FLU SV mRNA-024 study group
Affiliations Expand
- PMID: 42875682
- DOI: 10.1007/s40121-026-01462-w
Abstract
Introduction: Influenza vaccines targeting both hemagglutinin (HA) and neuraminidase (NA) might offer broader protection than current vaccines, which primarily target HA. This randomized phase 2 study evaluated the immunogenicity and safety of an investigational mRNA-based trivalent seasonal influenza vaccine encoding HA and NA from A/H1N1, A/H3N2, and B/Victoria (FLUm3HA-3NA).
Methods: Participants aged 18-64 years (younger adults) or 65-85 years (older adults) received one of several mRNA vaccine formulations-each containing different influenza A and B HA mRNA doses-or an age-appropriate licensed seasonal influenza vaccine as a comparator. Four formulations per age cohort were tested in part 1 of the study, and one formulation per age cohort in part 2. Day-29 hemagglutination inhibition (HI) and NA inhibition (NI) responses were assessed as primary and secondary endpoints, respectively, safety/reactogenicity as the secondary, and virus neutralization as the tertiary endpoint.
Results: A total of 250 younger and 260 older adults were vaccinated in part 1; 161 and 162, respectively, in part 2. All FLUm3HA-3NA formulations induced HI, NI, and neutralizing responses above baseline. In part 1, HI responses against A/H1N1 and A/H3N2 were similar or higher after FLUm3HA-3NA than after comparator vaccination in both age groups. For B/Victoria, HI responses were lower or similar versus comparator vaccination in younger adults and similar or higher in older adults. In part 2, HI responses were similar or higher with FLUm3HA-3NA versus comparators for A/H1N1 and A/H3N2, and lower for B/Victoria in both age groups. In both study parts and both age groups, NI titers were higher for all three strains with FLUm3HA-3NA versus comparators, and neutralizing titers were similar or higher for A/H1N1 and A/H3N2 and similar for B/Victoria. No safety concerns were identified.
Conclusions: FLUm3HA-3NA induced HI, NI, and neutralizing responses, with an acceptable safety profile. The results support further development, including optimization of the influenza B HI response.
Trial registration: ClinicalTrials.gov: NCT06431607.
Keywords: Adverse events; Hemagglutination inhibition assay; Hemagglutinin, influenza; Neuraminidase; Neuraminidase inhibition assay; Next-generation influenza vaccine; Virus neutralization; mRNA vaccine.