Moderna COVID-19 Vaccine

Kathryn Dzintars, Pharm.D., BCPS

VACCINE TYPE

  • Effective April 19, 2023, the Moderna monovalent COVID-19 vaccine is no longer recommended for use; all doses to be given moving forward will be with the bivalent vaccine. The bivalent vaccine is not licensed for any use but remains under Emergency Use Authorization for all individuals 6 months of age and older.
  • The Moderna COVID-19 vaccine (mRNA-1273) is a lipid nanoparticle-encapsulated, nucleoside-modified messenger RNA vaccine that encodes the SARS-CoV-2 spike glycoprotein.
    • Primary series: Single dose, 0.5 mL
    • An additional bivalent vaccine dose for patients > 65 years of age or those who are immune compromised can be given at least 4 months after the previous bivalent dose.
  • Catch-up vaccination:
    • Individuals 6 months through 5 years previously vaccinated with the Moderna vaccine
      • One previous dose: give a single dose, 0.25 mL, one month after being given the Moderna vaccine
      • Two previous doses: give a single dose, 0.2 mL, at least 2 months after being given the Moderna vaccine
    • Individuals 6 years of age and older previously vaccinated with one or more doses of the Moderna vaccine
      • 6 - 11 years: give a single dose, 0.25 mL, at least 2 months after being given the Moderna vaccine
      • 12 - 64 years: give a single dose, 0.5 mL, at least 2 months after being given the Moderna vaccine
      • ≥ 65 years: give a single dose, 0.5 mL, at least 2 months after being given the Moderna vaccine
        • One additional dose, 0.5 mL, may be administered at least 4 months after the previous bivalent dose
  • Mandatory requirements for the administration of mRNA-1273 under the EUA are as follows:
    • The vaccine is authorized in patients ≥ 6 months of age.
    • The vaccination provider must give the individual receiving the Moderna COVID-19 vaccine or their caregiver the “Fact Sheet for Recipients and Caregivers” before receiving the Moderna COVID-19 vaccine.
    • Vaccine providers must include vaccine information in the state’s or local jurisdiction’s Immunization Information System or other designated systems.
    • Vaccine providers are responsible for reporting certain events to the Vaccine Adverse Events Reporting System (VAERS):
      • Vaccine administration errors, whether or not associated with an adverse event
      • Serious adverse events include death, life-threatening, inpatient hospitalization/prolonged hospitalization, persistent or significant incapacity, and congenital anomaly/birth defects.
      • Cases of multisystem inflammatory syndrome (MIS) in children and adults
      • Cases of COVID-19 that result in hospitalization and death
    • Vaccine providers are responsible for responding to FDA requests for information about vaccine administration errors, adverse events, cases of MIS in adults and children, and cases of COVID-19 that result in hospitalization or death following administration of the Moderna or Pfizer-BioNTech COVID-19 Vaccine to recipients.

INDICATIONS

ACIP RECOMMENDATIONS

  • On December 19, 2020, ACIP voted in favor of the interim recommendation for using the Moderna COVID-19 vaccine for individuals ≥ 18 years of age.
  • The EUA fact sheet for recipients and caregivers should be provided to vaccine recipients, and recipients should be counseled on local and systemic reactions.
  • On August 31, 2022, ACIP supported the Moderna BIVALENT booster for individuals ≥ 18 years of age in those who have completed their primary series for additional protection against the Omicron BA.4/BA.5 variants.

FORMS

Brand Name

Preparation

Manufacturer

Route

Form

Dosage

Cost

Moderna COVID-19 Vaccine, BIVALENT (dark blue cap)

25 mcg SARS-Cov-2 S-protein encoded mRNA (Original) PLUS 15 mcg SARS-Cov-2 S-protein encoded mRNA (Omicron Ba.4/BA.5)

Moderna

IM

Vial

0.5 mL

N/A

Moderna COVID-19 Vaccine, BIVALENT (dark pink cap)

5 mcg SARS-Cov-2 S-protein encoded mRNA (Original) PLUS 5 mcg SARS-Cov-2 S-protein encoded mRNA (Omicron Ba.4/BA.5)

Moderna

IM

Vial

0.2 mL

N/A

PATHOGEN DIRECTED PROTECTION

DOSE/ADMINISTRATION

Adult PRIMARY SERIES

  • Single dose, 0.5 mL

Adult BOOSTER

  • An additional bivalent vaccine dose for patients > 65 years of age or those who are immune compromised can be given at least 4 months after the previous bivalent dose.

Pediatric PRIMARY SERIES

  • For patients ≥ 12 years of age
    • Single dose, 0.5 mL
  • For patients 6 - 11 years of age
    • Single dose, 0.25 mL
  • For patients 6 mos through 5 years
    • 2 doses, 0.25 mL each (dose 1 at month 0, dose 2 at month 1)

Pediatric BOOSTER

  • A single 0.2 mL dose can be given to immunocompromised pediatric patients.

ADVERSE DRUG REACTIONS

GENERAL

  • Overall, the Moderna vaccine is well-tolerated without serious adverse events reported to the FDA in the preliminary phase 3 trial information.
  • The incidence of adverse events is higher with administering the second dose of the vaccine.

COMMON

  • Pain, redness, and swelling at the injection site.
  • Fever
  • Fatigue
  • Headache
  • Chills
  • Diarrhea
  • Muscle and joint pain

RARE

  • At least 226 cases of myocarditis or pericarditis have been reported in patients ≤ 30 years of age, and cases are being investigated in at least 250 more reports.
    • Occurs after administration of the second dose of the vaccine
    • This adverse event remains rare, but the incidence rate is higher than expected in those ages 16 - 24 years.
    • Cases have predominantly been male, and the median age was 24 years.
    • Greater than 80% of cases have been resolved.
    • Myocarditis or pericarditis should be considered in patients developing acute chest pain, shortness of breath or heart palpitations within a week after vaccination.

VACCINE/DRUG INTERACTIONS

  • No vaccine/drug interactions have been identified at this time.

CONTRAINDICATIONS

  • Do not administer the Moderna COVID-19 vaccine to individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Moderna COVID-19 vaccine.

IMMUNE RESPONSE

  • The highest neutralization titers were obtained on days 29 and 57, confirming the need for a two-dose series.
    • Dose #2 elicited a robust immune response.
    • The serum-neutralizing activity was detected by two methods (binding antibody and neutralizing responses) in all 45 participants in a phase 1 trial[7].
  • The complete immune response is still being elucidated.
  • While vaccine effectiveness has been sustained against the need for hospitalization, reporting from the New York City area suggests vaccine effectiveness against infection has declined from 92% to 80%. These decreases were significantly worse in nursing home residents (74.7% to 53.1%).

CLINICAL EFFICACY

An ongoing, placebo-controlled, observer-blinded safety and efficacy trial in individuals ≥ 18 years of age is being conducted in the U.S.

  • 30,420 participants were randomized 1:1 to receive 2 doses, 28 days apart, of either placebo or the mRNA-1273 vaccine.
    • Follow-up for efficacy and safety will continue for 24 months after the second dose of the vaccine.
  • The primary endpoints were vaccine efficacy against COVID-19, safety, and immunogenicity.
  • The per-protocol set included 28,208 patients who received injections (14,134 in the vaccine group; 14,073 in the placebo group).
  • There were 11 cases of COVID-19 disease onset at least 7 days after the second dose in those receiving active vaccine compared to 185 cases of COVID-19 disease in those patients assigned placebo.
  • Similar vaccine efficacy was noted among subgroups, including age, sex, race, ethnicity and baseline body mass index.
  • The most common adverse effects were injection site pain, fatigue and headache.
  • The overall incidence of adverse effects was low and similar between the vaccine and placebo groups. Adverse effects were enhanced with the second dose.
  • In an ongoing open-label, non-randomized study in Israel, it has been reported that there are increased neutralizing antibodies (including those against Delta and Omicron variants) 2 weeks after receiving a second booster dose.

OTHER INFORMATION

  • Vaccination providers must report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, serious adverse events, multisystem inflammatory syndrome (MIS) cases in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Moderna COVID-19 vaccine.
  • More than 200 cases of myocarditis or pericarditis have been reported within one week of receiving the second vaccine dose of the mRNA vaccines. It most often occurs in males, whose median age is 24. While the incidence is rare, these rates are higher than expected. Anyone developing chest pain, shortness of breath or heart palpitations within 1 week of receiving the second dose of the mRNA vaccine should be evaluated.
  • The vaccine efficacy of the bivalent booster is unknown. EUA was granted based on limited human trials that displayed acceptable immunogenicity and safety.

Basis for recommendation

  1. Fact Sheet for Healthcare providers administering the vaccine, EUA for the Moderna COVID-19 Vaccine to prevent COVID-19.https://www.fda.gov/media/144637/download (Accessed 5/3/2023)

    Comment:
    Fact Sheet for Providers administering vaccine: Emergency Use Authorization (EUA) of the Moderna COVID-19 Vaccine to Prevent Coronavirus Disease 2019. Preliminary Phase 3 clinical trial data is included here, pending publication of additional trial data.


  2. Use of COVID-19 Vaccines in the United StatesInterim Clinical Considerations, https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vac... (accessed 5/3/2023).

    Comment:
    This page will have the latest recommendations, interim if not yet incorporated in a formal FDA approval.


References

  1. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2021;69(5152):1653-1656.  [PMID:33382675]

    Comment: MMWR report providing ACIP interim recommendations endorsing the Moderna EUA from the FDA. The committee agreed that robust clinical trial data support the administration of the two-dose vaccine series on Day 0 and Day 28 for the prevention of COVID-19 disease in those 18 years of age and older.

  2. Tenforde MW, Self WH, Naioti EA, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(34):1156-1162.  [PMID:34437524]

    Comment: An evaluation of 1,129 patients who completed the 2-dose vaccine series had sustained vaccine effectiveness against hospitalization over a 24 week period. Effectiveness was 86% through 2 - 12 weeks and fell to 84% from 13 - 24 weeks. However, investigators noted that ongoing monitoring is necessary as new variants continue to emerge.

  3. Rosenberg ES, Holtgrave DR, Dorabawila V, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status - New York, May 3-July 25, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(34):1150-1155.  [PMID:34437517]

    Comment: In an evaluation of vaccine effectiveness in the state of New York, the overall age-adjusted vaccine effectiveness against hospitalization remained stable (91.9% - 95.3%) while the age-adjusted vaccine effectiveness against infection decreased from 91.7% to 79.8%. This evaluation provides evidence for the need for a booster dose of the vaccination.

  4. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant - National Healthcare Safety Network, March 1-August 1, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(34):1163-1166.  [PMID:34437519]

    Comment: Evidence that vaccine effectiveness declined significantly with the emergence of the delta variant in nursing home residents. From March - May 2021, vaccine effectiveness was 74.7% compared to only 53.1% during June-July 2021. An additional dose of the COVID-19 vaccine is recommended to boost immunity.

  5. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020;383(20):1920-1931.  [PMID:32663912]

    Comment: This is the Phase 1, dose-escalation, open-label trial that included 45 adult participants, age 18 - 55, who received 2 doses of the mRNA-1273 vaccine, 28 days apart. Vaccine doses were 25 mcg, 100 mcg or 250 mcg. Higher doses elicited higher antibody responses. Serum neutralizing activity was detected in all participants after two vaccinations. The most common adverse events included fatigue, chills, headache, myalgias and pain at the injection site. Adverse events were higher with the second dose.

  6. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals. (Accessed 5/3/2023).

    Comment: Press release announcing recommendations for a second booster dose to be given 4 months after the initial booster dose in patients over the age of 50, or those aged 12 and over with immunocompromising conditions. In an ongoing open-label, non-randomized study in Israel, it is reported that there are increased neutralizing antibodies (including those against Delta and Omicron variants) were reported 2 weeks after receiving a second booster dose.

  7. https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-.... (Accessed 5/3/2023).

    Comment:

    American Academy of Pediatrics discussion on the CDC confirmation of more than 220 cases of myocarditis or pericarditis in those age 30 and younger occurring within 1 week of receiving the second dose of the COVID-19 mRNA vaccines. Although this incidence is rare, it is higher than what is expected. Greater than 80% of patients have made a full recovery. The CDC recommends that myocarditis or pericarditis be considered in any patient who develops acute chest pain, heart palpitations, and/or shortness of breath within 1 week of receiving their second vaccine dose.

  8. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html (accessed 5/3/2023).

    Comment:
    CDC recommendations for those who should receive booster vaccination after receiving the primary series. If the Moderna vaccine was the primary series, a booster dose is recommended 6 months after the initial 2-dose series. The booster vaccine can be any of the three approved COVID-19 vaccines in the US (Janssen, Moderna, Pfizer).


  9. FDA EUA update. Accessed 5/5/2023

    Comment:
    Emergency use authorization for the Moderns BIVALENT vaccine. It is recommended for use in individuals 18 years of age or older. It can be given two months after completion of the primary COVID vaccine series or two months after receipt of a previous booster.


  10. https://assets.modernatx.com/m/17d17b09d117ca22/original/EUA-COVID-19-Vacc.... Accessed 5/5/2023

    Comment:
    The updated EUA from April 2023, providing simplified dosing recommendations using only the bivalent COVID vaccine formulation.


Last updated: May 10, 2023