The effectiveness of the 2024-2025 messenger RNA COVID-19 vaccines (Pfizer-BioNTech, Moderna) and the Novavax COVID-19 vaccine, emergency authorized in August 2024 against the prevalent JN.1 subvariants, was corroborated in a study associating the vaccines with reduction in related emergency department visits, hospitalizations, and deaths.1
"Both authorizations were based on nonclinical data," observed Yi Du, PhD, of the Nebraska Department of Health and Human Services in Lincoln, and colleagues. "We present clinical evidence for the durability of protection provided by these updated vaccines over a 7-month period, during which circulating SARS-CoV-2 variants were predominantly JN.1 descendants."
The investigators accessed multiple records systems, including the Nebraska Electronic Disease Surveillance System and Hospital Discharge Data System, to identify 237,203 individuals receiving one of the 3 vaccines between August 22, 2024, and April 16, 2025 (86,594 Moderna, 148,429 Pfizer-BioNTech, 2180 Novavax). There were 12,860 SARs-CoV-2 infections in the cohort, 3330 related emergency department visits, 1566 related hospitalizations, and 189 related deaths.
Du and colleagues used a time-dependent Cox regression model to compare outcomes of vaccinated and unvaccinated populations. In addition to comparing same-day events to avoid temporal changes in disease incidence, they controlled for such potentially confounding variables as time since previous vaccination and/or infection and demographic factors such as sex, age, race, ethnicity, and socioeconomic status.
The investigators reported that the vaccines were comparable on the outcome measures and against different subvariants. Overall, vaccine effectiveness was 44.7% (95% CI, 37.7-50.9%) against infection at 4 weeks post vaccination. Effectiveness against infection declined to 35.5% (30.2%-40.5%) at 10 weeks and to 16.7% (8.4%-24.2%) 20 weeks after vaccination. Effectiveness against emergency department visit was 45.1% (28.9%-57.6%) at 4 weeks, declining slightly to 42.9% (32.5%-51.7%) at 10 weeks and 39.1% (13.4%-57.2%) at 20 weeks. The vaccine effectiveness for preventing hospitalization or death was 57.3% (42.6%-68.1%) at 4 weeks, 49.7% (39.2%-58.4%) at 10 weeks, and 34.0% (7.0%-53.1%) at 20 weeks.
They noted that although effectiveness against infection was similar to that of the 2023-2024 formula, the effectiveness against hospitalization and death appeared slightly lower, acknowledging that the estimates had "considerable uncertainties."
"The updated 2024-2025 COVID-19 vaccines provided effective protection, particularly against severe disease, although their effectiveness waned over time," Du and colleagues concluded.
What You Need to Know
Updated 2024–2025 COVID-19 vaccines provided meaningful protection—especially against severe disease—even as immunity gradually waned over several months.
All three vaccines (Moderna, Pfizer-BioNTech, Novavax) showed comparable performance against JN1 subvariants, reducing infections, emergency visits, hospitalizations, and deaths in a large real-world cohort of more than 230,000 people.
Despite continued evidence of safety and effectiveness, vaccination rates remain low—including among health care professionals—raising concern among experts about preventable severe outcomes.
In accompanying commentary, Robert Califf, MD, of the Division of Cardiology in the Department of Medicine at Duke University School of Medicine in Durham, North Carolina, commended the investigators on confirming the effectiveness of the vaccines, with methodologies "that, while imperfect, are the best we can do short of another RCT [randomized clinical trial]."2
The findings are consistent with previous studies, Califf points out, in that although less effective than the initial vaccines in reducing symptomatic infection, "the boosters produced a larger and highly clinically significant reduction in serious outcomes, including emergency department visits, hospital and intensive care unit admissions, and deaths."
Califf expressed particular concern that low rates of vaccination, despite evidence of safety and effectiveness, are not only found in the general public but among health care professionals. "Given this clear conclusion, it seems especially concerning that active clinical professionals, highly educated in biomedical subjects, are not availing themselves of a free intervention that reduces risks of death and hospitalization."
References
1. Du Y, Paritala S, Xu Y, Maloney P, Lin DY. Durability of 2024-2025 COVID-19 vaccines against JN.1 subvariants. JAMA Intern Med. Published online October 27, 2025. doi:10.1001/jamainternmed.2025.5465
2. Califf RM. Evidence, opinion, and uncertainty about COVID-19 vaccines. JAMA Intern Med. Published online October 27, 2025. doi:10.1001/jamainternmed.2025.5462
