Moderna announced today that its investigational combination vaccine against influenza and COVID-19, mRNA-1083, has successfully met all primary endpoints in a Phase 3 clinical trial, demonstrating superior immune responses compared to currently licensed vaccines.
The trial evaluated approximately 8,000 participants across two age cohorts: adults 65 years and older, and adults 50 to 64 years of age. In both groups, a single dose of mRNA-1083 elicited statistically significantly higher immune responses against three influenza virus strains (H1N1, H3N2, and B/Victoria) and against SARS-CoV-2, compared to standard vaccines administered separately.
"Combination vaccines have the potential to reduce the burden of respiratory viruses on health systems and pharmacies, as well as offer people more convenient vaccination options that could improve compliance and provide stronger protection from seasonal illnesses," said Stéphane Bancel, Chief Executive Officer of Moderna.
Superior Immune Response Data
In the 65 years and older cohort, mRNA-1083 was compared to co-administered Fluzone HD, an enhanced influenza vaccine, and Spikevax, Moderna's licensed COVID-19 vaccine. The Geometric Mean Ratios (GMRs) of the mRNA-1083 group compared to the Fluzone HD group for the influenza strains were:
- 1.155 (95% CI: 1.094, 1.220) for A/H1N1
- 1.063 (95% CI: 1.007, 1.122) for A/H3N2
- 1.118 (95% CI: 1.070, 1.167) for B/Victoria
For SARS-CoV-2 protection, the GMR of mRNA-1083 compared to Spikevax for the Omicron XBB.1.5 variant was 1.641 (95% CI: 1.526, 1.765), indicating a 64.1% higher immune response.
In the 50 to 64 years age cohort, mRNA-1083 was compared to co-administered Fluarix, a standard dose influenza vaccine, and Spikevax. The GMRs for the influenza strains were:
- 1.414 (95% CI: 1.333, 1.500) for A/H1N1
- 1.380 (95% CI: 1.310, 1.454) for A/H3N2
- 1.216 (95% CI: 1.163, 1.270) for B/Victoria
The GMR against SARS-CoV-2 Omicron XBB.1.5 was 1.308 (95% CI: 1.219, 1.404), showing a 30.8% higher immune response compared to Spikevax.
The vaccine also met non-inferiority criteria against the B/Yamagata strain of influenza in both age cohorts, though this strain has largely disappeared from circulation, leading the WHO to recommend its exclusion from 2024/2025 vaccine compositions.
Safety and Tolerability Profile
The trial data showed that mRNA-1083 had an acceptable tolerability and safety profile. Most solicited adverse reactions were grade 1 or 2 in severity, consistent with reactions observed with the licensed comparator vaccines. The most commonly reported side effects included:
- Injection site pain
- Fatigue
- Myalgia (muscle pain)
- Headache
Vaccine Composition and Development
mRNA-1083 combines components of mRNA-1010, Moderna's seasonal influenza vaccine candidate, and mRNA-1283, the company's next-generation COVID-19 vaccine candidate. Both of these investigational vaccines have independently demonstrated positive Phase 3 clinical trial results.
This development represents a significant milestone in Moderna's respiratory vaccine portfolio, as the company is now the first to report positive Phase 3 results for a combination flu and COVID-19 vaccine.
Public Health Implications
Combination vaccines could significantly streamline vaccination efforts, potentially increasing compliance by reducing the number of shots needed. This is particularly important for vulnerable populations such as older adults, who face higher risks from both influenza and COVID-19.
Dr. Bancel emphasized that this achievement builds on "the momentum of positive Phase 3 data across our respiratory portfolio" as the company continues to "address significant unmet medical needs and advance public health."
Next Steps
Moderna plans to present the detailed Phase 3 clinical data for mRNA-1083 at an upcoming medical conference and submit it for publication in a peer-reviewed journal. The company has also indicated it will engage with regulatory authorities on next steps toward potential approval.
If approved, this combination vaccine could be available for the 2025-2026 respiratory virus season, potentially simplifying vaccination campaigns and improving protection against multiple respiratory pathogens with a single administration.
