Pfizer-BioNTech COVID-19 Vaccine

Administration

Vaccine

• Pfizer-BioNTech COVID-19 Vaccine. Comirnaty, mRNA BNT162b2

Authorized for Use in

• US FDA (full approval), Health Canada, EU EMA, UK, WHO EUL, Australia TGA

Age

• ≥ 12 yrs in US/Canada/EU. ≥ 18yrs most other countries.
• 5-11 year old authorization for pediatric dose (10 μg) in US/Canada.
• Three dose series for age <5 yrs; EUA in expected end Q2 2022.

Type

• Lipid nanoparticle (LNP) encapsulated mRNA

Primary Dosing

• 0.3 mL IM (30 µg); 2 doses 3-8 weeks apart. 8 weeks preferred for ages 12-64.  3 weeks preferred for >65 yrs, immunocompromised, and persons who need rapid protection due to increased concern about current community transmission or risk of severe disease.

• Moderate and severe immunocompromise: third primary dose (0.3 mL; 30 µg) 28 days after dose 2. WHO EUL prefers 1-3 months.

Primary Dosing in Ages 5-11 Years

• 0.2 mL IM (10 µg) pediatric preparation; 2 doses 21 days apart (indefinite delay is acceptable).  No data on longer interval in this age group.
• Moderate and severe immunocompromise:  Additional primary dose (dose 3, 0.2 mL; 10µg): at least 28 days after dose 2. 

First Booster Dosing

• US guidelines presented; wide national variations regarding boosters.
• 0.3 mL IM  (30 µg) same as primary dose in persons aged >12 years, 5 months after completion of primary series.
• >Moderate and severe immunocompromise this is dose 4 (30 µg) to be given 3 months after dose 3.
• Pfizer vaccine (30 µg) can be used to boost a primary series of Moderna or Janssen/J&J vaccine in approved age groups.
• For children 5-11 years no booster doses are recommended, including in immunocompromised persons.
• WHO EUL recommendation--Booster at 4-6 months after dose 2 with mRNA vaccine. Consider EUL vectored vaccine for 2nd primary or subsequent booster doses.
• Three doses of mRNA vaccine is the only current effective strategy against the Omicron variant

Optional Second Booster Dosing

• US guidelines presented; wide national variations regarding boosters. These CDC recommended options are without formal ACIP review. Supporting clinical data limited to 1 Israeli cohort over age 60
• Optional:  0.3 mL IM (30 μg) in healthy persons aged >50 years, 4 months after first booster dose of either mRNA vaccine. Dose 4 for this population.
• Optional: 0.3 mL IM (30 μg) in moderately and severely immunocompromised persons aged ≥12, 4 months after the first booster dose of either mRNA vaccine. Dose 5 for this population.
• Pfizer vaccine (30 μg) can be used to boost a primary series of Moderna or Janssen/J&J vaccine in approved age groups.
• A person is up to date with their COVID-19 vaccination if they have received all recommended doses in the primary series and one booster when eligible. Getting a second booster is not necessary to be considered up to date at this time.  Up to date status alone affects recommendations for quarantine/isolation. 
• WHO EUL recommendation--subsequent boosters not yet considered.

Interchangeability

• Use same vaccine for all primary doses if possible. 
• Pfizer vaccine (30 ug) can be used to boost a primary series of Moderna or Janssen/J&J vaccine in approved age groups.
• 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.

Special Situation

• mRNA vaccines: For persons who inadvertently received the booster dose before their third primary dose, regardless of type of vaccine received as the booster dose, administer a Pfizer vaccine or a Moderna vaccine (100 µg) as the fourth dose (third primary) at least 3 months after the third dose. 

Storage

• Store frozen at -90°C to -60°C (-130°F to -76°F) until expiration date or at 2-8°C (36-46°F) for up to 1 month.

Efficacy

Overall against symptomatic disease

• 95% overall efficacy against symptomatic disease in Phase 3 trials pre-delta. Specific vaccine efficacy (VE) data against beta, gamma no longer relevant. 8-12 week interval from dose 1 to dose 2 superior VE compared to original 3 week interval.

Real world against hospitalization

• VE by vaccine (delta era): against hospitalization Moderna 95%, Pfizer 80%, J&J 60%. Several non-CDC US studies with VE against delta hospitalization >90% at 6 months. 94% in >1 million Israelis with predominant alpha. 2-doses have 88% VE against delta and 93% VE against alpha. Variety of international trials vary from 40-88% against infection with delta variant when followed for 6 months or more clear downward trend over time since vaccination past 6 months. Waning immunity against hospitalization for delta only definitive for >65 years of age.

Pediatric

• 100% in age 12-15 yrs, higher neutralizing titers than age 16-25 yrs. Two doses spaced by 21 days showed comparable nAb titers to 16-25 year old. In age 5-11 years. 90.7% vaccine efficacy with no myocarditis but small N.

Against severe disease / death

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

Against asymptomatic infection / transmission

• 70-90% in asymptomatic infection with alpha variant. 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

• 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.  Risk of myocarditis in 12-39 year olds decreased with 8 week interval between dose 1 and dose 2.  As of January 31, 2022, approximately 1,270 cases of myocarditis have been confirmed among mRNA vaccine (Pfizer and Moderna) recipients. Myocarditis is rarely reported after the booster dose. Among more than 39,000 reports of adverse events to VAERS, 37 cases of myocarditis were reported with an incidence of cases per million doses administered by age cohort (Pfizer; Moderna) as follows: 18-24 years (4.1; 8.7); 25-29 years; 1.1; 1.2), and 30-39 years (1.7; 1.5). The baseline annual incidence of any cause of myocarditis is 8 cases per million, with a peak incidence of 18 per million in persons aged 15-18 years; two-thirds of cases typically occur in males.

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 (dose 3), 28 days post primary series with same mRNA vaccine and a booster 3 months after dose 2. 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.