What are the recommendations for administering the Moderna (mRNA-1273) Spikevax (M-Spikevax) BA.4/BA.5 vaccine?

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Last updated: November 10, 2025View editorial policy

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Moderna Spikevax BA.4/BA.5 Bivalent Booster Administration

All persons aged ≥5 years should receive a bivalent mRNA COVID-19 vaccine booster dose (Moderna Spikevax BA.4/BA.5) at least 2 months after completion of any FDA-approved primary series or monovalent booster doses. 1, 2, 3

Vaccine Composition and Mechanism

  • The Moderna bivalent booster contains 25 μg ancestral mRNA spike protein and 25 μg of Omicron BA.4/BA.5 mRNA spike protein (total = 50 μg) 1, 2
  • The mRNA delivers genetic instructions to cells, resulting in temporary expression of both the original and Omicron BA.4/BA.5 spike proteins, triggering antibody and cellular immune responses 2
  • The mRNA does not enter the cell nucleus or interact with DNA, and is degraded shortly after protein production 2

Eligibility and Timing

Administer the bivalent booster at least 2 months after the last COVID-19 vaccine dose (whether primary series or monovalent booster). 1, 2, 3

  • For persons who recently had SARS-CoV-2 infection, consider delaying the booster dose by 3 months from symptom onset or positive test result 2, 3
  • This recommendation applies to all persons aged ≥5 years who completed any FDA-approved or FDA-authorized primary series 1, 2

Administration Technique

Administer intramuscularly at a 90-degree angle into the deltoid muscle of the upper arm for adolescents and adults, or the anterolateral aspect of the thigh for young children. 1, 4

Specific Technical Requirements:

  • Use a 22-25 gauge needle, 1-1½ inches in length for adolescents and adults to ensure proper muscle penetration 4
  • For children aged 5-11 years, the anterolateral thigh is the preferred site 1
  • Never use the buttock for vaccine administration due to risk of sciatic nerve injury and decreased immunogenicity 1, 4
  • Insert the needle into the injection site and pull back the plunger—if blood appears, withdraw and select a new site 1

Safety Protocols

Use sterile, disposable needles and syringes for each injection, never reusing or sharing equipment between patients. 1, 4

  • Wash hands with soap and water or use alcohol-based hand rub between each patient 1, 4
  • Gloves are not required unless the provider will contact potentially infectious body fluids or has open hand lesions 1, 4
  • Discard used sharps immediately in labeled, puncture-proof containers without recapping 1, 4
  • Never mix different vaccines in the same syringe unless specifically licensed for such use 1, 4

Expected Reactogenicity

Moderate, transient local and systemic reactions occur more frequently with Moderna vaccines and are more common after booster doses than primary series. 5, 6, 7

Common Adverse Events:

  • Fatigue, chills, headache, myalgia, and injection site pain are the most frequently reported symptoms 5, 8
  • Reactogenicity is dose-dependent and more common in younger adults (30-39 years) and females 6, 8
  • Approximately 50.7% of recipients report any adverse event in the first 0-3 days after vaccination 8
  • Serious adverse events are rare, with similar incidence to placebo groups in clinical trials 7

Critical Safety Consideration:

Myocarditis is a rare risk after mRNA COVID-19 vaccination, primarily affecting adolescent and young adult males, with highest risk among males aged 16-19 years (137 per million). 2

Clinical Rationale

The bivalent BA.4/BA.5 formulation was developed because monovalent vaccine effectiveness against COVID-19-associated hospitalization declined from 49% at 14-149 days after dose 3 to 34% at ≥150 days during the BA.4/BA.5 period 2, 3. Modeling demonstrates that vaccination coverage similar to influenza vaccine would reduce hospitalizations and deaths by >20% and >15%, respectively 1. The bivalent formulation expands immune protection against currently circulating Omicron variants while maintaining protection against the original strain 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Role of mRNA in COVID-19 Vaccines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

COVID-19 Vaccine Boosters and Continued Protection Against COVID-19

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Safe Injection Practices

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Reactogenicity Study of mRNA Vaccines Against COVID-19].

Archivos de prevencion de riesgos laborales, 2023

Research

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

The New England journal of medicine, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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