Interim Effectiveness of 2025-2026 mRNA-1283 and BNT162b2 COVID-19 Vaccines Against COVID-19-Related Outcomes Among Adults Aged ≥ 65 Years in the United States.

Publication date: Jun 24, 2026

The 2025-2026 COVID-19 vaccine season introduced updated formulations targeting the LP. 8.1 lineage. This interim analysis assessed absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged ≥ 65 years. This retrospective study used linked electronic health record and administrative claims data through January 31, 2026. Adults ≥ 65 years who received the mRNA-1283 or BNT162b2 2025-2026 COVID-19 vaccine were matched to unvaccinated individuals. Inverse probability of treatment weighting was applied to each vaccine’s matched cohorts to balance covariates. Each vaccine was evaluated independently against its own unvaccinated comparator group. aVE against COVID-19-related hospitalization and medically attended COVID-19 was estimated using Cox proportional hazards models; aVE = 100 cD7 (1 - hazard ratio). We identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients ≥ 65 years. aVE (95% confidence interval [CI]) of mRNA-1283 against COVID-19-related hospitalization and medically attended COVID-19 was 59. 3% (39. 0%, 72. 9%) and 42. 0% (35. 0%, 48. 3%) among adults ≥ 65 years and 66. 9% (45. 9%, 79. 8%) and 50. 2% (42. 1%, 57. 2%) in ≥ 75 years, respectively. The aVE (95% CI) of BNT162b2 against COVID-19-related hospitalization and medically attended COVID-19 was 48. 3% (32. 4%, 60. 5%) and 41. 2% (36. 2%, 45. 8%) in ≥ 65 years and 45. 9% (26. 0%, 60. 4%) and 44. 0% (37. 8%, 49. 6%) in ≥ 75 years, respectively. This study provides the first real-world evidence that mRNA-1283 was associated with protection against COVID-19-related hospitalization and medically attended COVID-19 among vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the continual burden of COVID-19 in this population.

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Concepts Keywords
Disease BNT162b2
Models COVID-19
mRNA-1283
Older adults
Vaccine effectiveness

Semantics

Type Source Name
disease MESH COVID-19
drug DRUGBANK Isoxaflutole
disease MESH Long Covid
disease MESH Dis
disease MESH hos
drug DRUGBANK Coenzyme M
disease MESH death
drug DRUGBANK Trestolone
disease MESH included
drug DRUGBANK Cefradine
disease MESH CED
disease MESH as1
disease MESH emergency
disease MESH plan
disease MESH asthma
pathway KEGG Asthma
disease MESH cancer
disease MESH cerebrovascular disease
disease MESH chronic kidney disease
disease MESH liver disease
disease MESH cystic fibrosis
disease MESH diabetes mellitus
disease MESH obesity
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH influenza
drug DRUGBANK Dimercaprol
disease MESH SMDs
disease MESH SMD
disease MESH HRs
drug DRUGBANK Methionine
disease MESH char
disease MESH ICD
disease MESH infection
drug DRUGBANK Ethionamide
drug DRUGBANK Ilex paraguariensis leaf
drug DRUGBANK Serine
drug DRUGBANK Indoleacetic acid
pathway REACTOME Reproduction
disease MESH hcp

Original Article

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