JAMA Analyzes Protection of 2025-2026 COVID Vaccines Against Latest SARS-CoV-2 Variants
The Journal of the American Medical Association published an analysis on September 2, 2025, evaluating the protection offered by the 2025-2026 COVID-19 vaccines against the latest SARS-CoV-2 variants in the United States. According to the article, the updated vaccines target emerging Omicron subvariants LP.8.1 and JN.1 to address challenges posed by evolving virus strains.
The 2025-2026 COVID-19 vaccines are designed to provide targeted protection against the latest SARS-CoV-2 variants, specifically the Omicron subvariants LP.8.1 and JN.1, according to an analysis published September 2, 2025, in the Journal of the American Medical Association (JAMA). The article, titled “SARS-CoV-2 Variants Challenge Surveillance Efforts and COVID-19 Vaccines,” evaluates how well these updated vaccines are expected to perform amid the evolving viral landscape in the United States.
Vaccine effectiveness against hospitalization during that period was estimated at 40%, with a 95% confidence interval ranging from 27% to 51%, sustained between 90 and 179 days post-vaccination, according to surveillance reports cited in the JAMA analysis.
The 2025-2026 vaccine formulations include Comirnaty, an mRNA vaccine targeting the LP.8.1 subvariant for children ages 5 to 11 with risk factors, and Nuvaxovid, an adjuvanted protein subunit vaccine aimed at the JN.1 subvariant for adults 65 and older as well as individuals aged 12 to 64 with underlying risk conditions. Nuvaxovid is administered as a 0.5 mL intramuscular injection, with doses given at least two months apart following previous vaccination, according to official vaccine guidelines. For unvaccinated individuals aged 12 to 64 who received the 2024-2025 Novavax vaccine, two doses of the updated formulation are recommended. The Nuvaxovid vaccine requires refrigerated storage between 2°C and 8°C, per manufacturer specifications.
Real-world data from the 2024-2025 vaccine season demonstrated moderate protection against infection, emergency department visits, and hospitalizations caused by JN.1 subvariants. Despite the emergence of new variants, the 2024-2025 vaccines reduced severe outcomes, supporting the rationale for updating vaccine compositions to address LP.8.1 and JN.1 in the current cycle.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (CDC ACIP) has issued recommendations for the 2025-2026 vaccination period. Individuals aged 5 to 64 years are advised to receive one dose of the age-appropriate 2024-2025 COVID-19 vaccine, while adults 65 years and older should receive two doses spaced six months apart. Immunocompromised persons who are unvaccinated are recommended to complete a multidose initial series followed by a booster dose at least six months later, with a minimum interval of two months between doses. Those who previously completed a vaccine series should receive two doses of the 2024-2025 vaccine if immunocompromised. Policy options under consideration include maintaining multidose series for children ages 6 months to 4 years and immunocompromised populations.
Specific dosing schedules have been outlined for special populations. Immunocompromised individuals who have not been vaccinated are advised to receive two doses of Nuvaxovid three weeks apart, followed by an additional dose six months later. For those who have received one or two doses of mRNA vaccines, completing a three-dose series with mRNA vaccines before receiving a Nuvaxovid dose six months afterward is recommended. Individuals who have completed the initial series should receive two Nuvaxovid doses six months apart, with a minimum of eight weeks after the last dose. Additional doses may be administered at intervals of two months or more based on ongoing clinical needs. Adults 65 and older are advised to receive two doses annually, with additional doses for those unvaccinated with Novavax or who are immunocompromised.
Historical data underscore the impact of COVID-19 vaccination efforts. From 2020 through 2024, vaccinations are estimated to have averted approximately 2.5 million deaths in the United States, with a range between 1.4 million and 4.0 million, and saved an estimated 15 million life-years, according to modeling studies cited in the JAMA article. Most life-years saved, about 76%, occurred among people over 60 years of age. Globally, 13 billion doses had been administered by the end of 2023, with 67% of the population completing the primary vaccine series.
Policy discussions for 2025-2026 include a universal vaccination approach for individuals six months and older, encompassing multidose initial series, or a more targeted approach focusing on high-risk populations. Semi-annual dosing schedules, involving two doses per year, are recommended for adults 65 and older and immunocompromised individuals. Additional doses may be considered under shared clinical decision-making frameworks, particularly for unvaccinated immunocompromised persons or those undergoing immune-ablative therapies.
The JAMA analysis highlights ongoing challenges in SARS-CoV-2 variant surveillance and vaccine adaptation as the virus continues to evolve. The updated 2025-2026 vaccines reflect efforts to maintain protection levels amid shifting variant prevalence and to reduce the burden of severe COVID-19 outcomes in vulnerable populations.
