COVID Vaccines Comparison Guide
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The recommended COVID-19 vaccines for the 2025-2026 season are updated formulations from Pfizer-BioNTech (Comirnaty, LP.8.1), Moderna (Spikevax, mNEXSPIKE1), and Novavax (Nuvaxovid), all designed to target the JN.1 Omicron lineage, with a preference for the LP.8.1 strain which reflects the most common circulating variant right now. There is no strong preference between these vaccines when multiple options are available; choice is largely based on age, risk factors, and availability1.
Current Recommendations
- Adults ages 65 and older, and those aged 5-64 with at least one underlying risk factor, are specifically recommended to receive a dose of the updated vaccine4.
- All persons ages 6 months and older may receive a 2025-2026 COVID-19 vaccine, particularly those at high risk, immunocompromised, or with household exposure to high-risk persons2.
- For previously vaccinated individuals, a single dose given at least two months after the last dose is typical for most patients8.
- For children younger than age 2 who have never received a COVID-19 vaccine, the current recommendation is to complete an initial series (usually two doses 1 month apart with Moderna's Spikevax)1.
Vaccine Types and Differences
| Vaccine Brand | Platform | Target Variant | Age Indication | Unique Feature | Efficacy (LP.8.1) |
|---|---|---|---|---|---|
| Comirnaty (Pfizer) | mRNA | LP.8.1 Omicron | ≥5 (high risk); ≥65 | Codes full spike protein | Robust neutralization4 |
| Spikevax (Moderna) | mRNA | LP.8.1 Omicron | ≥6 months (gen pop) | Codes full spike protein | Effective, similar to Pfizer3 |
| mNEXSPIKE1 (Moderna) | mRNA | LP.8.1 Omicron | ≥12 (high risk) | Only N-term/RBD domains | Similar clinical response1 |
| Nuvaxovid (Novavax) | Protein Subunit | JN.1 Omicron | ≥12 (high risk) | Adjuvanted, non-mRNA | Estimated equivalent to mRNA1 |
- All the vaccines have been reformulated to closely match LP.8.1, which is a JN.1-lineage Omicron variant most prevalent in wastewater and clinical cases as of September 20253.
- The mRNA vaccines (Pfizer and Moderna) encode the spike protein, while Novavax contains recombinant spike protein with an adjuvant, meaning it does not use genetic coding technology3.
- Data suggests that the LP.8.1-adapted vaccines induce strong neutralizing antibody responses and are expected to better prevent symptomatic infection and severe disease with current variants compared to previous vaccine versions4.
Side Effects and Considerations
- Side effects for the new formulations are reported to be similar to previous iterations: mostly mild to moderate, and transient (e.g., soreness, fatigue, fever)2.
- For those who are immunocompromised, additional doses may be recommended at longer intervals1.
Summary Table
| Population | Recommended Vaccine Formulation | Dosing | Notes |
|---|---|---|---|
| Adults ≥65 | Any (Pfizer, Moderna, Novavax) | 1 dose | Highly recommended |
| Age 6 months – 64 (high risk) | Any (Pfizer, Moderna, Novavax) | 1 dose | High risk includes comorbidities |
| Ages 6–23 months (primary) | Moderna (Spikevax) | 2 doses 1 month | If never vaccinated before |
| Immunocompromised (any age) | Any, possibly repeat dosing | ≥2 months apart | Follow CDC guidance |
| General population <65, healthy | Shared decision making | 1 dose | Optional, discuss with provider |
Key Takeaways
- The 2025–2026 COVID-19 vaccine formulas all target the most current and prevalent Omicron variants5.
- Safety, immunogenicity, and efficacy are comparable between mRNA and protein-based technologies for the recommended LP.8.1 strain4.
- For most individuals, any available vaccine may be selected according to age and risk—there is no official preferential product at this time2.
References
- https://secure.medicalletter.org/TML-article-5121a
- https://www.aap.org/en/patient-care/covid-19/covid-19-vaccine-frequently-asked-questions/
- https://www.healthpartners.com/blog/covid-19-vaccine-doses/
- https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontechs-comirnatyr-receives-us-fda-approval
- https://www.fda.gov/vaccines-blood-biologics/industry-biologics/covid-19-vaccines-2025-2026-formula-use-united-states-beginning-fall-2025
- https://www.aarp.org/health/conditions-treatments/updated-seasonal-covid-vaccines/
- https://www.cnn.com/2025/08/30/health/covid-19-vaccine-eligibility-medical-conditions-wellness
- https://coronavirus.health.ny.gov/2025-2026-covid-19-immunization-guidance-adults
- https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-topline-data-demonstrating
- https://www.cdph.ca.gov/Pages/public-health-for-all/publichealthforall.aspx
- https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/10-levi-COVID-508.pdf
- http://www.publichealth.lacounty.gov/media/coronavirus/vaccine/index.htm
- https://www.youtube.com/watch?v=u9mQ6CzuUOs
- https://www.uchealth.org/today/everything-you-need-to-know-about-the-2025-26-covid-19-vaccine-and-flu-shots/
- https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Panagiotakopoulos-COVID-508.pdf
- https://health.ucdavis.edu/news/headlines/covid-is-surging-again-what-you-need-to-know-about-the-new-vaccine/2025/09
- https://www.cdc.gov/covid/vaccines/stay-up-to-date.html
- https://www.politico.com/news/2025/08/22/covid-shot-hhs-recommendations-fall-00519315