Effectiveness of 2025-2026 mRNA-1283 and BNT162b2 COVID-19 Vaccines Against COVID-19 Related Hospitalizations and Medically-Attended COVID-19 Among Adults Aged >= 65 years in the United States

BackgroundThe 2025-2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [≥]65 years. MethodsThis retrospective study used linked electronic health record and administrative claims data through Jan 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 vaccines 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 x (1 - hazard ratio [HR]). ResultsWe identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [≥]65 years. The aVE (95% confidence interval) 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 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. ConclusionsThis is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.