2024-2025 COVID-19 Vaccines Provided Moderate Protection Against JN.1 Variants

Why It Matters

The findings confirm that current vaccines still reduce severe outcomes despite modest efficacy, guiding public‑health recommendations and future vaccine composition decisions.

Key Takeaways

• Overall VE 40% against JN.1 hospitalizations.
• Protection rises to ~52% after 90 days.
• Older adults (65+) see 45% effectiveness.
• Vaccinated proportion low among cases (11%).
• Study limited by sequencing gaps and prior immunity.

Pulse Analysis

The JN.1 sublineage emerged as the dominant SARS‑CoV‑2 strain in the United States during the 2024‑2025 winter, succeeding the XBB family and prompting the FDA to authorize updated vaccine formulations. Moderna and Pfizer leveraged the KP.2 spike protein, while Novavax introduced a JN.1‑specific antigen, reflecting a strategic shift toward lineage‑focused immunogens. This evolution illustrates the virus’s capacity for rapid antigenic drift, compelling manufacturers to anticipate future mutations and streamline regulatory pathways for timely updates.

In the IVY Network’s prospective case‑control study, immunocompetent adults who received a 2024‑2025 vaccine experienced a 40% reduction in COVID‑19‑related hospitalizations, with effectiveness climbing to 52% between 90 and 179 days post‑vaccination. Older adults (≥65) fared slightly better, achieving 45% overall protection. The median interval since vaccination was shorter among cases, suggesting waning immunity may influence outcomes. Although the study did not adjust for prior infection or earlier vaccine doses, the data provide a realistic snapshot of real‑world performance against a moderately immune‑evading variant.

For policymakers and health systems, the moderate yet durable protection underscores the importance of maintaining booster campaigns, especially for high‑risk populations. Continuous genomic surveillance and rapid vaccine redesign remain critical to counteract emerging lineages. As the pandemic transitions into an endemic phase, integrating variant‑specific effectiveness data into public‑health messaging can sustain vaccine confidence and optimize resource allocation for future immunization strategies.

2024-2025 COVID-19 Vaccines Provided Moderate Protection Against JN.1 Variants

Sabrina McCrear · Fact‑checked by: Christina Mattina · February 19 2026

COVID‑19 vaccination showed effectiveness in reducing hospitalizations and severe disease outcomes associated with the SARS‑CoV‑2 JN.1 lineage, according to a recent study published in JAMA Network Open.^1

COVID‑19 remains a public health threat. Between 2024 and 2025, an estimated 380,000–540,000 patients were hospitalized and 44,000–63,000 deaths occurred in the United States. The rise in cases was driven primarily by the newer JN.1 variant, which succeeded the XBB lineage. In response, the FDA approved updated vaccines from Moderna and Pfizer (based on the KP.2 lineage) and an updated Novavax vaccine (based on the JN.1 lineage) in 2024. The JN.1 descendants continued to evolve throughout the 2024‑2025 season, prompting researchers to reassess vaccine effectiveness.

Study Design

The case‑controlled study prospectively enrolled patients ≥ 18 years old admitted to hospitals in the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network between September 1 2024 and April 30 2025. A total of 8,493 patients were enrolled: 1,888 COVID‑19 cases and 6,605 controls. The median age was 66 years; 51.1 % were female and 48.9 % male.

Patient Demographics

• Hispanic or Latino: 12.5 % (1,061)

• Non‑Hispanic Black: 22.4 % (1,905)

• Non‑Hispanic White: 57.5 % (4,883)

• Non‑Hispanic other race: 5.1 % (434)

• Unknown race/ethnicity: 2.5 % (210)

COVID‑19 cases were younger than controls (median 65 vs 71 years; P < .001) and had a lower Charlson Comorbidity Index (median 4 vs 5; P < .001).

Vaccination Status & Effectiveness

• Among case patients, 216 (11.4 %) had received a 2024‑2025 COVID‑19 vaccine, compared with 1,224 (18.5 %) of controls.

• In the 6,131 immunocompetent adults, overall vaccine effectiveness against COVID‑19–associated hospitalization was 40 % (95 % CI 27‑51 %).

• Median time since vaccination: 80 days (IQR 43‑137) for cases; 108 days (IQR 66‑151) for controls.

Effectiveness by interval after vaccination:

• 7‑89 days: 34 % (95 % CI 14‑49 %)

• 90‑179 days: 52 % (95 % CI 34‑65 %)

In immunocompetent adults ≥ 65 years:

• Overall: 45 % (95 % CI 31‑56 %)

• 7‑89 days: 44 % (95 % CI 25‑59 %)

• 90‑179 days: 51 % (95 % CI 31‑66 %)

Prior studies have shown that COVID‑19 vaccination reduced the risk of long COVID by 36 % in adolescents aged 12‑17 years.^2

Limitations

• Declining hospitalization numbers limited long‑term effectiveness estimates.

• The analysis did not adjust for prior infections or previous vaccinations that could influence effectiveness.

• Incomplete viral sequencing, limited national generalizability, and residual confounding may affect the findings.

Authors’ Conclusion

“During a season without major antigenic changes to circulating SARS‑CoV‑2 viruses, we found sustained protection from COVID‑19 vaccines through at least 90‑179 days after vaccination. Monitoring COVID‑19 vaccine effectiveness, including stratifying by SARS‑CoV‑2 lineage and spike‑protein mutations, remains important to guide vaccine composition and recommendations.”

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References

1. Ma KC, Webber A, Lauring AS, et al. Estimated effectiveness of 2024‑2025 COVID‑19 vaccination against severe COVID‑19. JAMA Netw Open. 2026;9(2):e2557415. doi:10.1001/jamanetworkopen.2025.57415

2. McCormick B. COVID‑19 vaccination linked to lower risk of long COVID in adolescents. AJMC. November 3 2025. Accessed February 18 2026. https://www.ajmc.com/view/covid-19-vaccination-linked-to-lower-risk-of-long-covid-in-adolescents/