Moderna Reports mNEXSPIKE COVID-19 Vaccine Study Results

Cambridge, Massachusetts, United States, November 11, 2026

Real-World Study Shows Improved Comparative Effectiveness

The study evaluated the comparative effectiveness of mNEXSPIKE and Comirnaty among U.S. Veterans aged 65 years and older who received an LP.8.1-formulated vaccine between August 27, 2025, and January 31, 2026. Participants were followed for up to 150 days or until May 1, 2026. The primary endpoint was medically attended COVID-19, which included hospitalizations, emergency department visits, urgent care consultations, outpatient visits and antiviral treatment. According to the published findings, mNEXSPIKE was associated with 35.9% relative vaccine effectiveness against medically attended COVID-19 compared with Comirnaty, with a 95% confidence interval of 20.4% to 49.7%. The analysis also found a 47.0% relative vaccine effectiveness against COVID-19-associated hospitalization, with a 95% confidence interval of 5.4% to 74.8%. Point estimates consistently favored mNEXSPIKE across the individual components of medically attended COVID-19. These findings provide comparative evidence on the performance of the two vaccines in an older adult population during a respiratory virus season. However, the results represent relative effectiveness estimates from an observational study and should not be interpreted as proof that one vaccine is universally superior for every individual.

Cardiovascular Outcomes Highlight Broader Health Considerations

In addition to evaluating COVID-19-related medical visits and hospitalizations, researchers conducted an exploratory analysis examining hospitalizations involving major adverse cardiovascular events (MACE). These events included myocardial infarction, stroke and heart failure. The analysis found that mNEXSPIKE was associated with 39.3% relative vaccine effectiveness against MACE-related hospitalization compared with Comirnaty, with a 95% confidence interval of 11.8% to 57.0%. This exploratory finding is relevant because COVID-19 infection has been associated with complications involving underlying chronic conditions, including cardiovascular disease. Older adults with pre-existing health conditions may face additional risks when experiencing severe respiratory infections. The researchers therefore examined cardiovascular outcomes to better understand the potential broader health implications of COVID-19 prevention. Nevertheless, the cardiovascular analysis was exploratory, and the findings do not establish that mNEXSPIKE directly prevents heart attacks, strokes or heart failure. Further research will be necessary to investigate these associations and determine their clinical significance. The results nevertheless contribute to the growing body of real-world research examining the wider health consequences of COVID-19 infection among older populations.

Study Design, Limitations and Clinical Significance

The investigation used a retrospective, active-comparator matched cohort study design involving VHA-enrolled veterans aged 65 years and older. Participants receiving mNEXSPIKE or Comirnaty were matched according to their home county and vaccination calendar week. Researchers also applied inverse probability of treatment weighting to reduce potential differences between the comparison groups. The study was supported by Moderna, which contributed to the study design, data interpretation, manuscript preparation, review and approval, and the decision to submit the research for publication. However, the company did not conduct the study or collect, manage or analyze the data. The investigators acknowledged several limitations, including the possibility of residual confounding from differences in testing behavior, undocumented previous infections and vaccine availability. Additionally, the predominantly older male veteran population may limit the generalizability of the findings to women and the broader U.S. population. The observational nature of the research means that the results demonstrate associations rather than establishing causation. Despite these limitations, the large study population provides valuable comparative effectiveness information for healthcare professionals evaluating COVID-19 vaccination options for older adults. Overall, the publication in JAMA Network Open represents an important addition to the real-world evidence surrounding mRNA COVID-19 vaccines and protection against severe disease. Moderna’s findings highlight the potential clinical relevance of mNEXSPIKE in older adults while reinforcing the need for continued research into vaccine effectiveness, hospitalization outcomes and associated health complications. As COVID-19 continues to pose health risks for vulnerable populations, large-scale comparative studies can help inform clinical discussions and public health decision-making. The findings also demonstrate the importance of real-world evidence in complementing clinical trial data and understanding vaccine performance across different patient populations.

Source: Moderna press release