VACCINE TYPE

• 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.
  • Two-dose series, given one month (28 days) apart
  • 28 days is recommended between the first and second dose for moderate to severely immunocompromised individuals, those > 65 years of age, and anyone who needs rapid protection due to increased concern for high community transmission. This interval can be increased to 8 weeks in those concerned with a small risk of myocarditis (males aged 12 - 39 years).
  • A third dose can be administered to select immunocompromised patients a minimum of 28 days after the initial 2-dose series (see below).
  • A booster dose is recommended for all individuals 6 months of age or older at least 2 months after the initial 2-dose series is completed.
• The U.S. FDA issued an Emergency Use Authorization (EUA) to permit the emergency use of the Moderna COVID-19 vaccine for active immunization to prevent COVID-19 in individuals 6 months of age through 17 years.
  • 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 either 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.
      • This also includes cases of the multisystem inflammatory syndrome (see SARS-CoV-2, COVID-19 module for details).
• There are no data on the interchangeability of COVID-19 vaccines. If the primary series is initiated with the Moderna product, the primary should be completed with the Moderna product.
  • Booster doses can be provided with any of the COVID-19 vaccines approved for use in the U.S.; the mRNA vaccines are preferred. (Janssen, Moderna, Pfizer)
• On August 12, 2021, the EUA was modified to include the administration of a third dose after the initial 2-dose primary series to certain immunocompromised patients (solid organ transplant, active treatment of solid or hematologic malignancies, CAR-T or prolonged immunosuppressive therapy, advanced/untreated HIV infection, active treatment with prednisone ≥20 mg/day)
  • The additional dose should be the same vaccine product as the original two-dose series.
  • Administer the additional dose at least 28 days after completing the initial two-dose series (this is based on expert opinion only).
• On October 21, 2021, the CDC recommended booster vaccines for most individuals.
  • The following are eligible for a booster:
    • It should be given to anyone 6 months years of age and older
    • Booster doses should be administered at least 2 months after completing the primary vaccination series..
    • A second booster dose should be offered to individuals 4 months after the initial booster who are over the age of 50, or are 18 years or older with an immunocompromising condition.
    • On August 31, 2022, the FDA issued an Emergency Use Authorization for Moderna BIVALENT (Original PLUS Omicron BA.4/BA.5)
      • The bivalent vaccine can be given to individuals ≥ 6 months of age as a single booster after either the completion of primary vaccination with any authorized monovalent COVID vaccine or after receipt of the most recent booster dose with any authorized monovalent COVID vaccine.
        • Monovalent boosters will no longer be available.
  • Booster doses can be provided with any of the COVID-19 vaccines approved for use in the U.S. (Janssen, Moderna, Pfizer); the mRNA vaccines are preferred.
• FDA fully approved vaccine for ages ≥ 18 years, January 31, 2022.
• On June 17th, 2022, the FDA expanded the age limit to include children > 6 months of age to 17 years.

INDICATIONS

FORMS

PATHOGEN DIRECTED PROTECTION

• SARS-CoV-2

DOSE/ADMINISTRATION

ADVERSE DRUG REACTIONS

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.
  • This translates to 94.1% vaccine efficacy in preventing COVID-19 disease.
• 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

• It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of the multisystem inflammatory syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Moderna COVID-19 vaccine.
  • See https://vaers.hhs.gov/reportevent.html for instructions on reporting.
• 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, and the median age is 24 years. 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 12/20/2022)

   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 12/20/2022).

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

References

3. 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.
   

4. 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.
   

5. 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.
   

6. 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.
   

7. 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.
   

8. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals. (Accessed 12/20/2022).

   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.
   

9. https://www.fda.gov/media/161318/download. Accessed 12/20/2022.

   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://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html (accessed 12/20/2022).

    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).
    
    
    

11. https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-.... (Accessed 12/20/2022).

    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.