Moderna’s late-stage investigational influenza COVID-19 vaccine was shown to be noninferior in comparison to other vaccines and elicited better immune responses. The results were published in JAMA today.1 “mRNA-1083 met noninferiority criteria and induced higher immune responses than recommended standard care influenza (standard and high dose) and COVID-19 vaccines against all 4 influenza strains (among those ages 50-64 y), the 3 clinically relevant influenza strains (among those aged ≥65 y), and SARS-CoV-2 (all ages),” the investigators wrote. 1
The Study’s Design and Parameters
This was a randomized, observer-blinded, active-controlled phase 3 study carried out in 146 sites exclusively in the US. It was divided into 2 different aged cohorts: individuals 65 years and older; and people 50-64 years old. In a substudy, those 65 years and older was also stratified into those aged 65 to 74 years or 75 years and older. 1
The study enrolled and vaccinated 8015 individuals. The data from this study provided safety and immunogenicity findings of the planned interim analyses after all participants had completed the day 91 visit. 1
“mRNA-1083 contained 5 mRNA sequences encoding membrane-bound hemagglutinin of 4 influenza strains (recommended for Northern Hemisphere 2023-2024 season) and the linked NTD-RBD of the SARS-CoV-2 S glycoprotein (Omicron XBB.1.5), encapsulated in lipid nanoparticles,” the investigators wrote. 1
Individuals were administered either the mRNA-1083 vaccine, or 1 of 2 standalone influenza vaccines plus a COVID-19 vaccine. 1
What You Need to Know
Moderna's combination vaccine induced a higher immune response than standalone influenza and COVID-19 vaccines, showing noninferiority and better performance against all influenza strains and SARS-CoV-2 in adults aged 50+.
The vaccine demonstrated an acceptable safety and tolerability profile, with data from over 8,000 participants in a Phase 3 US-based study.
While the vaccine met its immunogenicity goals, the FDA requested additional phase 3 influenza efficacy data, delaying full approval until 2026.
“mRNA-1083 increased hemagglutination inhibition and PsVNA GM antibody levels against each influenza (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) and SARS-CoV-2 strain at day 29 vs baseline…The primary immunogenicity objective was achieved in both substudies. Noninferiority of mRNA-1083 vs SD-IIV4 plus mRNA-1273 and HD-IIV4 plus mRNA-1273 was demonstrated against all vaccine-matched influenza and SARS-CoV-2 strains based on prespecified success criteria for GMR (97.5% CI lower bound >0.667) and seroconversion/seroresponse rate difference (97.5% CI lower bound >−10%),” the investigators wrote.1
The investigators pointed out a few potential benefits with the Moderna vaccine. “The mRNA platform used to develop mRNA-1083 has numerous advantages, including avoidance of egg adaptation–related changesas well as the breadth of immunity and T-cell responses for the influenza component (mRNA-1010),” they wrote. “Additionally, the rapid production and flexibility for updates to vaccine composition can ensure close matching to circulating influenza and SARS-CoV-2 virus strains. Further, the platform can quickly adapt to allow for timely and effective public health responses, especially in the face of emerging variants and strains.”
The Vaccine’s Status
Earlier this week, it was announced the FDA requested that Moderna provide more data for this vaccine. Specifically, the federal agency requested more phase 3 influenza efficacy data.2 Moderna had requested a full approval of the vaccine based upon its data from the phase 3 trials.2 In its quarterly earnings, Moderna says that with this recent FDA feedback, the company expects to extend its review timeline for the vaccine and is now targeting a potential approval in 2026.2
References
1. Rudman Spergel AK, Wu I, Deng W, et al. Immunogenicity and Safety of Influenza and COVID-19 Multicomponent Vaccine in Adults ≥50 Years: A Randomized Clinical Trial. JAMA. Published online May 07, 2025. doi:10.1001/jama.2025.5646
2.Moderna Reports First Quarter 2025 Financial Results and Provides Business Updates.Moderna May 1, 2025. Accessed May 2, 2025.
