Humoral Immunogenicity of mRNA-1010, an mRNA-Based Seasonal Influenza Vaccine, in Adults ≥50 Years

Abstract Background Seasonal influenza causes substantial morbidity and mortality worldwide. In a phase 3 study in adults ≥50 years, trivalent mRNA-1010 demonstrated superior efficacy versus a standard-dose (SD) seasonal influenza vaccine. This analysis reports humoral immunogenicity. Methods Participants were randomized 1:1 to a single dose of mRNA-1010 (37.5-µg) or licensed SD influenza vaccine. Immunogenicity was assessed in a pre-specified per-protocol subset. Anti-hemagglutinin antibody titers were measured by hemagglutination inhibition (HAI) and microneutralization (MN; subset) at baseline and Day 29 against vaccine-matched strains. Outcomes included geometric mean titers (GMTs), geometric mean fold rises (GMFRs) from baseline, and seroconversion rates (SCRs; ≥4-fold rise). Results The per-protocol immunogenicity subset included 2342 participants (mRNA-1010, n=1167; SD influenza vaccine, n=1175). mRNA-1010 induced higher levels of HAI antibody relative to SD influenza vaccine. mRNA-1010 increased HAI GMTs, with Day 29 GMFRs of 4.07 (A/H1N1), 4.70 (A/H3N2), and 3.14 (B/Victoria). GMR point estimates versus SD influenza vaccine exceeded 1.5 across all strains, with lower bounds (LBs) of 95% CIs all exceeding 1.4: 1.82 (95% CI; 1.69–1.97), 1.59 (1.48–1.71), and 1.67 (1.57–1.78), respectively. Similarly, SCR differences were positive; LBs >15: 27.95% (95% CI: 24.09-31.73), 19.99% (15.99-23.92), and 25.33% (21.65-28.95), respectively. mRNA-1010 elicited higher MN antibody responses versus SD influenza vaccine for all 3 strains. Conclusions In adults ≥50 years, a single dose of mRNA-1010 induced higher humoral immune responses against vaccine-matched influenza strains than licensed SD influenza vaccine. Together with previously reported results, these findings support mRNA-1010 as a seasonal influenza vaccine option in adults ≥50 years.