2024-2025 COVID-19 Vaccine Formulation
The FDA-approved 2024-2025 COVID-19 vaccines target the Omicron JN.1 lineage, with Moderna and Pfizer-BioNTech formulations based on the KP.2 strain and Novavax based on the JN.1 strain. 1
Current Vaccine Formulation
The 2024-2025 season vaccines represent an updated formulation that replaced the 2023-2024 XBB-sublineage vaccines, which are no longer circulating widely in the United States. 1, 2 The FDA approved these vaccines in August 2024 following ACIP's June 27,2024 recommendation for universal vaccination of all persons aged ≥6 months. 1
Who Should Receive the 2024-2025 Vaccine
ACIP recommends 2024-2025 COVID-19 vaccination for all persons aged ≥6 months to provide protection against currently circulating SARS-CoV-2 strains and reduce severe COVID-19-associated illness and death. 1, 2
Standard Dosing Schedule
For persons aged ≥5 years who are not immunocompromised: 1
- Previously vaccinated individuals: 1 dose of any 2024-2025 vaccine (Moderna, Pfizer-BioNTech, or Novavax for ages ≥12 years), administered ≥8 weeks after the last COVID-19 vaccine dose 1
- Unvaccinated individuals: 1 dose of Moderna or Pfizer-BioNTech, or 2 doses of Novavax (ages ≥12 years only) given 3-8 weeks apart 1
For children aged 6 months-4 years who are not immunocompromised: 1
- Unvaccinated: Moderna requires 2 doses (4-8 weeks apart); Pfizer-BioNTech requires 3 doses (3-8 weeks between doses 1-2, ≥8 weeks between doses 2-3) 1
- Previously vaccinated: Dosing depends on prior vaccine brand and number of doses received, ranging from 1-2 additional doses 1
Immunocompromised Patients
Moderately or severely immunocompromised persons require additional doses: 1
- Unvaccinated individuals aged ≥12 years should receive 3 doses of mRNA vaccine or 2 doses of Novavax 1
- After completing the initial series and receiving at least 1 dose of 2024-2025 vaccine, they may receive 1 additional dose at least 2 months later 1
- Further additional doses may be administered at ≥2-month intervals based on clinical judgment 1
Vaccine Effectiveness Data
The evidence supporting these recommendations comes from 2023-2024 vaccine data, which ACIP used to project effectiveness for the 2024-2025 formulation. 1
Against symptomatic infection: 1, 2
- 58% effectiveness against XBB-sublineage infection at 60-119 days post-vaccination 1, 2
- 37% effectiveness against JN.1-sublineage infection at 60-119 days post-vaccination 1, 2
- 49% effectiveness at 7-59 days after vaccination 1, 2
- Declines to 14% at 120-179 days after vaccination 1, 2
Against critical illness (more durable protection): 1, 2
The most recent high-quality evidence from 2025 confirms vaccine effectiveness of 68% against hospitalization for KP.2-targeted vaccines in a case-control study. 3
Evidence Quality and Clinical Context
The certainty of evidence is rated as low for most outcomes in adults and adolescents, and very low for infants and children, meaning the true effectiveness may differ from these estimates. 1, 2 However, the vaccines provide substantially better protection against severe outcomes (hospitalization, critical illness, death) than against mild infection, which is the most clinically relevant benefit for reducing morbidity and mortality. 2
Safety Considerations
Vaccine Safety Datalink surveillance identified two statistical signals during the 2023-2024 season: 1
- Guillain-Barré syndrome in persons aged ≥65 years (new signal, evidence inconclusive) 1
- Ischemic stroke in adults aged ≥50 years (similar to prior bivalent vaccine signal, cumulative data have not provided clear evidence of a safety problem) 1
The most recent 2025 evidence confirms myocarditis rates of 1.3-3.1 per 100,000 doses in male adolescents, with lower risk associated with longer dosing intervals. 3 Any theoretical vaccine adverse event risk must be weighed against the substantial benefits of preventing COVID-19 complications, including stroke. 1
Important Clinical Pitfalls
- Timing matters: Vaccine effectiveness is highest in the first 2 months after vaccination, with declining protection over time, particularly against hospitalization 2
- Don't delay in high-risk groups: Adults aged ≥65 years experience the highest rates of severe COVID-19 and derive the most cost-effective benefit from vaccination 1
- Immunocompromised patients need more doses: Standard single-dose recommendations do not apply to this population 1
- The 2024-2025 formulation is NOT interchangeable with prior formulations: Only the updated JN.1/KP.2-targeted vaccines provide protection against currently circulating strains 1