mRNA-1273 shows greater COVID-19 protection than NVX-CoV2705 in retrospective US cohort study
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Key Takeaway
Consider mRNA-1273's greater observed effectiveness versus NVX-CoV2705 in retrospective data, but note study limitations.
This retrospective matched cohort study analyzed data from a large US claims database, comparing COVID-19 outcomes in 69,140 mRNA-1273 recipients and 34,570 NVX-CoV2705 recipients who were matched on demographic and clinical factors. The population consisted of US insured adults aged 18 years or older, with follow-up from day 7 after vaccination through up to 180 days.
For the primary outcome of medically-attended COVID-19, mRNA-1273 showed an adjusted comparative vaccine effectiveness (cVE) of 31.7% (95% CI 23.4% to 39.1%) compared to NVX-CoV2705, with 706 events (1.02%) in mRNA-1273 recipients versus 512 events (1.48%) in NVX-CoV2705 recipients. For hospitalization with COVID-19, the adjusted cVE was 40.7% (95% CI 13.5% to 59.4%), with 61 events (0.09%) in mRNA-1273 recipients and 49 events (0.14%) in NVX-CoV2705 recipients. In recipients aged 65 years or older, adjusted cVE was 25.7% for medically-attended COVID-19 and 41.7% for hospitalization.
Safety and tolerability data were not reported in this analysis. Key limitations include the observational design, which cannot establish causality, potential residual confounding despite matching, reliance on claims data for outcome ascertainment, and lack of information on prior infection status or variant exposure. The study was conducted in a US insured population, which may limit generalizability.
For clinical practice, these findings suggest a potential effectiveness difference between these vaccine platforms in real-world use, but the retrospective nature and absence of safety data warrant cautious interpretation. The results may inform vaccine selection discussions while awaiting prospective comparative data.
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View Original Abstract ↓
Background: COVID vaccination with periodically 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). There is limited head-to-head real-world evidence comparing the effectiveness of these different approaches to prevention of severe outcomes with COVID-19. 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 or NVX-CoV2705 between Aug 31, 2024 and Feb 28, 2025 were eligible. Recipients were exactly 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 x (1-- hazard ratio). Results: Of 858,138 eligible mRNA-1273 recipients and 34,667 eligible 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% 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. Conclusions: 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.
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