mRNA-1283 Lowers COVID-19 Hospitalization Risk in Adults 65 and Older

Updated COVID-19 vaccination continued to protect older adults from hospitalization during the 2025-2026 season, even among those with substantial prior immunity, according to a study of mRNA-1283 (mNEXSPIKE; Moderna), a next-generation COVID-19 vaccine.¹

In a matched cohort analysis of linked electronic health record and claims data, mRNA-1283 showed an absolute vaccine effectiveness (aVE) of 59.3% against COVID-19–related hospitalization among 233,072 vaccinated adults 65 years and older, rising to 66.9% among those 75 years and older. BNT162b2 (Comirnaty; Pfizer-BioNTech), evaluated separately against its own unvaccinated comparison group among 422,610 vaccinated adults, showed an aVE of 48.3% against hospitalization in adults aged 65 years and older. The interim analysis was also published in Infectious Diseases and Therapy.²

The findings were presented at IDWeek 2026, held October 21 to 24, 2026, in Washington, DC. In this interview with The American Journal of Managed Care^® (AJMC^®), Nevena Vicic, MSc, director of global medical affairs for infectious diseases at Moderna and the study's lead author, discusses why the research focused on older adults, how to interpret the 2 vaccines' results side by side, and what payers and health systems should consider when planning vaccination strategies.

This transcript has been lightly edited.

AJMC: The study you're presenting offers the first real-world evidence on mRNA-1283 in adults 65 years and older, finding an absolute vaccine effectiveness of 59.3% against COVID-19–related hospitalization. Why was it important to study this population first, and what stood out to you in the results?

Vicic: Adults aged 65 years and older continue to bear a disproportionate burden of severe COVID-19, including hospitalizations and deaths, making them a particularly important population in which to evaluate vaccine effectiveness. What stood out was that mRNA-1283 demonstrated nearly 60% effectiveness against COVID-19–related hospitalization, even in a population where more than 80% had received a COVID-19 vaccine in the prior season. This highlights the additional protection that updated vaccination can provide, even in individuals with substantial preexisting immunity.

AJMC: Among adults 75 years and older, mRNA-1283's absolute vaccine effectiveness against COVID-19–related hospitalization was 66.9%. What do these findings suggest for protecting the oldest adults, who are at highest risk of severe disease?

Vicic: Adults aged 75 years and older are particularly vulnerable to severe COVID-19, often due to age-related changes in immune function and the presence of underlying medical conditions. The 66.9% effectiveness observed against COVID-19–related hospitalization is particularly encouraging and highlights the important role updated vaccination can play in protecting those at greatest risk of severe outcomes.

AJMC: The study used linked electronic health record and claims data, matching vaccinated individuals to unvaccinated ones and applying inverse probability of treatment weighting. What are the strengths and limitations of this approach compared with a clinical trial?

Vicic: Clinical trials show us how well vaccines work under controlled conditions, while real-world studies help us understand how they perform in everyday clinical practice, including in specific populations such as older adults with underlying health conditions. We used established statistical methods to make the vaccinated and unvaccinated groups as comparable as possible, although we cannot account for every potential difference. Together, clinical trials and real-world evidence provide a more complete picture of vaccine effectiveness to help inform health care decisions.

AJMC: Each vaccine was compared with its own unvaccinated cohort rather than head-to-head. How should clinicians interpret the mRNA-1283 and BNT162b2 results side by side?

Vicic: Both mRNA-1283 and BNT162b2 demonstrated effectiveness against COVID-19–related hospitalization during the 2025-2026 season, reinforcing the continued benefit of updated vaccination. Although we observed numerically higher effectiveness estimates for mRNA-1283, each vaccine was evaluated independently against its own unvaccinated comparison group, so these findings should not be interpreted as evidence of superiority of one vaccine over the other. Direct comparative effectiveness studies would provide further insights into potential differences between the vaccines.

AJMC: As real-world evidence on updated COVID-19 vaccines continues to emerge, what should payers and health systems take away from these findings when planning vaccination strategies for older adults?

Vicic: One of the most important takeaways is that COVID-19 continues to pose a meaningful clinical burden in older adults, and updated vaccination provides additional protection against hospitalization, even in populations with substantial prior immunity. For payers and health systems, these findings reinforce the value of prioritizing vaccination among older and high-risk adults, improving access and uptake, and using real-world evidence to inform prevention strategies. Ultimately, preventing severe disease and hospitalization remains one of the most important public health goals of COVID-19 vaccination.

AJMC: Why do you think it's important for clinicians, policymakers, and other stakeholders to attend a conference like IDWeek?

Vicic: IDWeek provides a unique opportunity for clinicians, researchers, and public health decision-makers to come together, critically evaluate emerging scientific evidence, and discuss how these findings can translate into clinical practice. With the infectious disease landscape continuously evolving, it's particularly important to share real-world evidence alongside clinical trial data so that decisions are informed by how interventions are actually performing in the populations we aim to protect.

Author Disclosures: Nevena Vicic, MSc, is an employee and stockholder of Moderna Inc. The study was funded by Moderna.

References

1. Vicic N, Bogdanov A, Hensler H, et al. 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. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.

2. Vicic N, Bogdanov A, Hensler H, et al. 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. Infect Dis Ther. Published online June 2026. doi:10.1007/s40121-026-01395-4