Moderna COVID-19 Vaccine

by David O. Freedman, M.D. last updated 2022-01-11 08:36:00.456076-05:00 © Antimicrobial Therapy, Inc.
Spikevax, mRNA-1273

Administration

Vaccine

  • Moderna COVID-19 Vaccine. Spikevax, mRNA-1273

Authorized for Use in

  • US FDA, Health Canada, EU EMA, UK, WHO EUL, Australia TGA

Age

  • ≥ 18 yrs (100 ug per dose) in USA/Canada/EU).
  • ≥ 12 yrs in Canada/EU (100 ug per dose)
  • Immunogenicity trials complete.  VE for age 12-17, 100% and in 6-11 year olds nAb titers 1.5X those of 16-25 year old group after 50 ug dose.  US EUA expected Q1 2022; myocarditis analysis pending.

Type

  • Lipid nanoparticle (LNP) encapsulated mRNA

Primary Dosing in Persons >12 Years

  • 0.5 mL IM (100 µg); 2 doses 28 days apart (indefinite delay is acceptable).
  • Not approved in US for ages 12-17.
  • Severe immunocompromise:  additional primary dose (100 µg; dose 3) 28 days after dose 2.
    • However give 50 µg as additional primary dose 2 months after a primary dose of Janssen/J&J.

Primary Dosing in Persons 5-11 Years

  • Not approved in this age group

Booster Dosing

  • US guidelines presented; wide national variations regarding boosters
  • 0.25 mL (25 µg)(half-primary (50 µg) dose) IM 5 months after completion of primary series in persons >18 years.
  • For immunocompromised this is dose 4 (50 µg) to be given 5 months after dose 3.  
    • CDC encourages use for the booster dose of the same product that was used for the primary series but states that any FDA authorized vaccine may be used if preferred; most experts recommend that all booster doses be with an mRNA vaccine regardless of vaccine used for the primary dose or doses. 

Interchangeability

  • Use same vaccine for all primary doses if possible.
  • Moderna vaccine (50 µg) can be used to boost a primary series of Pfizer or Janssen/J&J vaccine.
  • Three doses of mRNA vaccine is the only current effective strategy against the Omicron varian
  • CDC recommends that persons aged ≥ 18 years (including moderately or severely immunocompromised persons who received an additional primary dose) who were fully vaccinated with a WHO EUL vaccine not authorized/approved by US FDA or with a heterologous series composed of any FDA-authorized/approved or WHO EUL authorized vaccine are eligible to receive a single booster dose of the Pfizer vaccine (0.3 mL; 30 µg) at least 6 months after completion of their primary series under the existing age guidelines as for Moderna and Pfizer vaccines. Practically, either mRNA vaccine may be used for a booster in this situation.

Storage

  • Store frozen at -50°C to -15°C (-58°F to 5°F) until expiration date. 2-8°C (36-46°F) for up to 30 days

Efficacy

Overall against symptomatic disease

  • 94.1% and 90.9% in adults with comorbidities.
    • Overall efficacy against symptomatic disease in Phase 3 trials pre-delta. Specific vaccine efficacy (VE) data against beta, gamma no longer relevant.

Real world against hospitalization

  • VE by vaccine (delta era): against hospitalization Moderna 95%, Pfizer 80%, J&J 60%.
  • VE was 87.4% against infection, 95.8% against hospitalization, and 97.9% against death. VE was higher against symptomatic (88.3%) versus asymptomatic infection (72.7%) but was generally similar across age, sex, and racial/ethnic subgroups.

Pediatric

  •  VE for age 12-17, 100% and in 6-11 year olds nAb titers 1.5X those of 16-25 year old group after 50 ug dose.

Against severe disease / death

  • ~100%; rare breakthroughs mostly in >80 yrs of age. Delta era: 91-94% against death.

Against asymptomatic infection / transmission

  • Delta variant results in peak viral loads 1,000 times higher than the alpha variant and is equal between vaccinated and unvaccinated persons, but virus is cleared more rapidly in vaccinated persons.

Duration of efficacy after Primary or Booster Series

  • Efficacy after dose 2 appears negligible against the Omicron variant and data is not yet available for efficacy duration after a booster dose. 

Toxicities

Contraindications

  • Anaphylaxis or immediate allergic reaction (within 4 hours of administration) to a previous dose of an mRNA vaccine or separately to a vaccine constituent including polyethylene glycol (PEG) or polysorbate. Defer vaccination for 90 days after receipt of monoclonal or plasma therapy.

Precautions

  • Immediate allergic reaction (within 4 hours of administration) to any other vaccine or injectable therapy not related to a component of mRNA-COVID-19 vaccines or polysorbate. Persons with a reaction to a vaccine or injectable therapy that contains multiple components, one of which is PEG, another mRNA vaccine component or polysorbate, but in whom it is unknown which component elicited the immediate allergic reaction

Not contraindications

  • Food (including egg and gelatin), pet, insect, venom, environmental, latex, oral medications (including the oral equivalents of injectable medications) allergies; any other history of anaphylaxis not related to vaccine or injectables; or a family history of anaphylaxis. History of GBS in proximity to another vaccine.

Adverse effects

  • Anaphylaxis 5.0 per million doses; 90% within 30 minutes, 96% females. US vaccinees for the week following the first dose was: injection-site pain (67.8%), fatigue (30.9%), headache (25.9%), myalgia (19.4%), fever (8.6%), and joint pain (8.7%).
  • For vaccinees with 2 doses rates were much higher for dose 2: injection-site pain (72.3%), fatigue (53.9%), headache (46.7%), myalgia (44%), fever (29.5%), and joint pain (25.6%). Rates same for Pfizer and Moderna.
  • Mild myocarditis is rare but associated with mRNA vaccination almost exclusively in young males and mostly within a week after the 2nd dose. The
    highest incidence (12.6 cases per million) is in those younger than 40 years, with a peak incidence of 60 cases per million in males aged 12-24 years. Baseline rates of myocarditis in 15-18 males is 18 per million. No deaths have been reported and only a minority had abnormal echocardiograms; long term sequelae cannot be ascertained at present. VSD: incidence of selected serious outcomes (including acute myocardial infarction, Bell's palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome) was not
    significantly higher 1 to 21 days post vaccination compared with 22 to 42 days post vaccination.

Special Needs Populations

Pregnancy

  • Use. VE after 56 days of was 96% for any documented infection, 97% symptomatic infection and 89% for hospitalization in 20,000 Israeli women. No reproductive or development concerns (preliminary); risk of disease effect > known vaccine risk; endorsed for use by CDC, ACOG, AAP. No reported issues in 70,000 pregnancies to date in the USA. US Vaccine Safety Datalink (VSD) analyzed 105,446 unique pregnancies and 13,160 spontaneous abortions with no increased risk in mRNA vaccinees. No evidence of an increased risk for early pregnancy loss after vaccination in 14,000 Norwegian women.

Immunocompromised / HIV

  • Give additional primary dose (100 µg; dose 3), 28 days post primary series with same mRNA vaccine. Considered part of primary series in this population and not a booster.
  • Serology not indicated before or after.
  • Indicated for: Solid organ transplants, CAR-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation and on immunosuppression therapy), severe primary immunodeficiency, advanced or untreated HIV infection, active treatment with high-dose corticosteroids (i.e., ≥ 20 mg prednisone or equivalent per day), alkylating agents, antimetabolites, cancer chemotherapeutic agents classified as severely immunosuppressive, TNF inhibitors, and other biologic agents that are immunosuppressive or immunomodulatory.
    • When possible, mRNA vaccine doses (primary or additional) should be given at least 2 weeks before initiation of immunosuppressive therapies.