Comparative Effectiveness of mRNA-1273 Versus Protein-Based NVX-CoV2705 Vaccination on COVID-19-Related Outcomes Among Insured Adults in the United States During 2024-2025: A Retrospective Matched Cohort Study.

INTRODUCTION

COVID-19 vaccination with updated compositions remains important as SARS-CoV-2 continues to circulate, cause disease, and evolve. Available COVID-19 vaccines in the 2024-2025 season differed by platform, including mRNA-1273, an mRNA-based vaccine, and NVX-CoV2705, a recombinant protein-based vaccine and antigen composition (KP.2-targeted and JN.1-targeted, respectively). Limited real-world evidence exists comparing effectiveness in preventing severe COVID-19 outcomes. We compared mRNA-1273 with protein-based NVX-CoV2705 in insured US adults vaccinated during the 2024-2025 season.

METHODS

We conducted a retrospective matched cohort study in a large US claims database. Adults aged 18 years or older who received mRNA-1273 ("exposed") or NVX-CoV2705 ("reference") between August 31, 2024 and February 28, 2025 were eligible. Recipients were matched 2:1 on key demographic and clinical factors and then weighted with stabilized inverse probability of treatment weights. Outcomes were medically attended COVID-19 and hospitalization with COVID-19 from day 7 after vaccination through up to 180 days of follow-up. We calculated comparative vaccine effectiveness (cVE) as 100 × (1 - hazard ratio).

RESULTS

Of 1,156,441 mRNA-1273 recipients and 45,384 NVX-CoV2705 recipients, 69,140 and 34,570, respectively, entered the matched cohort. Median (Q1, Q3) follow-up was 180 (163, 180) days for mRNA-1273 and 180 (162, 180) for NVX-CoV2705. Medically attended COVID-19 occurred in 706 (1.02%) mRNA-1273 recipients and 512 (1.48%) NVX-CoV2705 recipients; adjusted cVE (95% confidence interval [CI]) was 31.7% (23.4%, 39.1%). Hospitalization with COVID-19 occurred in 61 (0.09%) and 49 (0.14%) recipients, respectively; adjusted cVE (95% CI) was 40.7% (13.5%, 59.4%). In the 47,754 mRNA-1273 recipients matched to 23,877 NVX-CoV2705 recipients aged ≥ 65, adjusted cVE (95% CI) was 25.7% (15.4%, 34.8%) against medically attended COVID-19 and 41.7% (14.3%, 60.4%) against hospitalization with COVID-19.

CONCLUSION

In this insured US adult population, mRNA-1273 demonstrated greater effectiveness against medically attended COVID-19 and hospitalization with COVID-19 than the protein-based NVX-CoV2705. These findings highlight the potential public-health importance of considering vaccine platform and variant selection when planning for upcoming seasons.