M-Spikevax (mRNA-1273.214) Dosage and Schedule
M-Spikevax (mRNA-1273.214) is administered as a single 50 μg booster dose at least 2 months after completion of any FDA-approved or FDA-authorized COVID-19 primary series or previous monovalent booster dose for adults aged ≥18 years. 1
Primary Series vs. Booster Dosing
M-Spikevax specifically refers to the bivalent formulation (mRNA-1273.214) containing equal amounts of spike mRNA from the ancestral SARS-CoV-2 strain and Omicron BA.4/BA.5 subvariants. 1 This is distinct from the original monovalent Spikevax (mRNA-1273) used for primary series vaccination. 1
- For primary series: The original monovalent Spikevax is used as a 2-dose series (or 3-dose for immunocompromised individuals), not M-Spikevax. 1
- For booster doses: M-Spikevax (bivalent BA.4/BA.5) is administered as a single 50 μg dose. 1
Timing Recommendations
- Minimum interval: Administer ≥2 months after the last dose of any COVID-19 vaccine (primary series or monovalent booster). 1
- Optional delay after infection: Individuals who recently had SARS-CoV-2 infection may consider delaying the booster by 3 months from symptom onset or positive test, though this is not required. 1
Special Populations
Immunocompromised Patients
- Immunocompromised adults follow the same booster dosing schedule (single 50 μg dose ≥2 months after last vaccine), but may have received a 3-dose primary series initially. 1
- These patients should also be considered for preexposure prophylaxis with monoclonal antibodies to supplement vaccine protection. 1
Patients on Immunomodulatory Therapy
For patients on certain immunosuppressive medications, timing adjustments may optimize vaccine response:
- Methotrexate: Consider holding for 1 week after each vaccine dose if disease activity permits. 1
- JAK inhibitors: Consider holding for 1 week after each vaccine dose regardless of disease activity. 1
- Subcutaneous abatacept: Hold for 1 week before and 1 week after the first dose only (total 2 weeks), but no adjustment needed for subsequent doses. 1
- Rituximab: Time administration 2-4 weeks after the final vaccine dose if disease control permits. 1
Important Clinical Considerations
Common pitfall: Do not confuse M-Spikevax (bivalent booster) with the original Spikevax (monovalent primary series vaccine). The bivalent formulation is only authorized for booster doses, not primary series. 1
Coadministration: M-Spikevax can be administered simultaneously with other vaccines, including influenza vaccine, without any required waiting period between doses. 2
Reactogenicity: Solicited adverse reactions occur in approximately 90% of recipients, similar to the original mRNA-1273 vaccine, with no new safety concerns identified. 3
Immunogenicity Data
The bivalent BA.4/BA.5 formulation demonstrates superior neutralizing antibody responses against Omicron subvariants compared to monovalent boosters, with GMC ratios of 1.53-1.68 against BA.1 variant. 3 Cross-neutralization extends to more recent variants including XBB.1.5, EG.5.1, BA.2.86, and JN.1. 4
Real-world effectiveness data from Nordic countries shows 67.8% (95% CI 63.1-72.5%) comparative vaccine effectiveness against COVID-19 hospitalization and 69.8% (95% CI 52.8-86.8%) against COVID-19-related death at 3 months post-vaccination in adults ≥50 years. 5