BNT162b2 COVID-19 Vaccine (BioNTech/Pfizer)

Kathryn Dzintars, Pharm.D., BCPS

VACCINE TYPE

  • On August 23, 2021, the FDA approved the Pfizer-BioNTech COVID-19 vaccine for individuals ≥ 16 years of age. It remains under the EUA for individuals aged 12 - 15 years and was expanded to include children aged 5 - 11 years at a reduced dose. On June 17th, 2022, the FDA recommended lowering the age eligibility to any child 6 months of age and older.
  • The Pfizer-BioNTech COVID-19 vaccine (BNT162b2; Comirnaty) is a lipid nanoparticle-formulated, nucleoside-modified RNA (mRNA) vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 spike protein.
    • Primary series: two-dose series, given 21 days apart
      • 21 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 out 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.
        • 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 (based on expert opinion only).
    • Booster dose:
      • Should be given to anyone aged 5 years and older.
      • Booster doses should be administered 5 months after completing the primary vaccination series. Booster doses can be administered at 3 months in the immunocompromised patient.
      • A second booster dose is recommended at least 4 months after the initial booster dose for individuals over the age of 50, and those aged 12 and over with certain types of immune compromise.
      • On August 31, 2022, the FDA approved the Emergency Use Authorization for Pfizer-BioNTech COVID-19 BIVALENT (Original + Omicron BA.4/BA.5).
        • The bivalent vaccine can be given to individuals ≥ 12 years 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.
  • The Emergency Use Authorization (EUA) remains in effect for the Pfizer-BioNTech COVID-19 vaccine for active immunization to prevent COVID-19 in individuals 5 - 15 years of age.
    • Mandatory requirements for the administration of BNT162b2 under the EUA are as follows:
      • The vaccination provider must give the individual receiving the Pfizer-BioNTech COVID-19 vaccine or their caregiver the “Fact Sheet for Recipients and Caregivers” before the individual receiving the Pfizer-BioNTech COVID-19 vaccine.
      • Vaccine providers must include vaccine information to 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 adverse events, inpatient hospitalization/prolonged hospitalization, persistent or significant incapacity, congenital anomaly/birth defects
        • Cases of the 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 Pfizer-BioNTech COVID-19 Vaccine to recipients.
  • There are limited data on the interchangeability of COVID-19 vaccines. If the primary series is initiated with the Pfizer-BioNTech product, the primary series should be completed with the Pfizer-BioNTech product.
    • Booster shots can be administered with any of the COVID-19 vaccines authorized in the U.S. (mRNA vaccines preferred; those aged 5 - 17 years can receive only the Pfizer-BioNTech vaccine).

INDICATIONS

ACIP RECOMMENDATIONS

  • On December 12, 2020, ACIP voted 11–0 (three recusals) in favor of the interim recommendation for using the Pfizer-BioNTech COVID-19 vaccine for individuals ≥ 16 years of age.
    • On May 10, 2021, ACIP voted to lower the recipient age to individuals ≥ 12 years of age.
    • FDA-approved vaccine for ages 12 and older, ACIP update 8/12/21
    • On November 2, 2021, ACIP unanimously voted to recommend vaccination to children 5 - 11 years of age at a reduced dose (10 mcg/0.2mL) in a 2-dose series administered 3 weeks apart.
    • On January 5, 2022:
      • ACIP voted to approve the use of a booster dose, five months after the initial series, to children ≥ 12 years of age.
      • A third dose of the Pfizer vaccine should be given four weeks after the 2-dose series to immunocompromised children aged 5 - 11.
    • On February 22, 2022, preliminary recommendations were made to potentially expand the dosing interval between doses #1 and #2, especially in adolescents and younger adults, to lessen the risk of myocarditis.
      • If immunocompromised, the original schedule should be kept.
    • On May 17, 2022, a booster dose was approved in children 5 - 11 years of age, five months after the initial series.
    • On June 17, 2022, the age eligibility was lowered to children 6 months of age and older.
  • On August 31, 2022, ACIP supported using the Pfizer BIVALENT booster for individuals ≥ 12 years of age in those who have completed their primary series for additional protection against the Omicron BA.4/BA.5 variants.
  • The EUA fact sheet for recipients and caregivers should be provided to vaccine recipients, and recipients should be counseled on local and systemic reactions.

FORMS

Brand Name

Preparation

Manufacturer

Route

Form

Dosage

Cost

Comirnaty (full-dose, purple cap)

SARS-Cov-2 S-protein 30µg encoded mRNA + lipid nanoparticle vaccine

Pfizer-BioNTech

IM

Vial

0.3 mL IM on Day 0 and Day 21

N/A

Comirnaty (reduced-dose, orange cap)

SARS-Cov-2 S-protein 10µg encoded mRNA + lipid nanoparticle vaccine

Pfizer-BioNTech

IM

Vial

0.2 mL IM on Day 0 and Day 21

N/A

Pfizer-BioNTech COVID-19 Vaccine, BIVALENT (full-dose, gray cap)

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

Pfizer-BioNTech

IM

Vial

0.3 mL

N/A

PATHOGEN DIRECTED PROTECTION

DOSE/ADMINISTRATION

Adult PRIMARY SERIES

  • This is a series of 2 vaccines given 3 weeks apart.
    • The first dose (0.3 mL) should be given on Day 0 and the second dose (0.3 mL) on Day 21.
    • 21 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 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 other individuals beginning 5 months after completing the initial 2-dose series.
  • There are no data on the interchangeability of the vaccines during the primary series.
    • If you receive the Pfizer-BioNTech vaccine on Day 0, the series should be completed with the Pfizer-BioNTech product.
  • Thaw instructions for undiluted vials:
    • Refrigerator: Once in the refrigerator, the vial(s) will thaw in 2-3 hours. Thawed vials can be stored at 2ºC to 8ºC (35ºF to 46ºF) for up to 10 weeks.
    • Room temperature: Vials may be stored at room temperature for 12 hours before the first puncture. After the first puncture, multiple-dose vials should be kept between 2ºC to 25ºC (35ºF to 77ºF). Multidose vials should be discarded 12 hours after the first puncture.
    • Once vials have been thawed, they cannot be refrozen.

Adult BOOSTER

  • Booster dose:
    • It should be given to anyone aged 12 years and older.
    • Booster doses should be administered five months after completing the primary vaccination series.
      • Immunocompromised patients should receive their booster at 3 months.
    • A second booster dose is recommended at least 4 months after the initial booster dose for individuals over the age of 50, and those aged 12 and over with certain types of immune compromise.

Pediatric PRIMARY SERIES

  • For patients ≥ 12 years of age, per the current EUA:
    • This is a series of 2 vaccines given 3 weeks apart. The first dose (0.3 mL) should be given on Day 0 and the second dose (0.3 mL) on Day 21.
    • 21 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 out to 8 weeks in those concerned with a small risk of myocarditis (males aged 12 - 39 years)
    • A third dose can be given 28 days after completion of the initial 2-dose series in select immunocompromised patients.
  • For patients 5 - 11 years of age, per the current EUA:
    • This is a series of 2 vaccines given 3 weeks apart. The first dose (0.2 mL) should be given on Day 0 and the second dose (0.2 mL) on Day 21.
    • This is a reduced dose compared to those ≥ 12 years of age and older.
    • A third dose can be given 28 days after completion of the initial 2-dose series in select immunocompromised patients.
  • For patients 6 months to 5 years of age, per the current EUA:
    • This is a series of 3 vaccines. The first dose (0.2mL) should be given on Day 0, followed by a second dose on Days 21 through 56. The third dose should be administered 8 weeks after the second dose.
    • This is a reduced dose compared to those 12 years of age and older.

Pediatric BOOSTER

  • A booster dose is recommended beginning at least 5 months after the completion of the initial two-dose (or three if immunocompromised) series for children 5 years of age and older.
    • Recommendations for the bivalent booster are not yet available.
  • A booster dose is not recommended at this time for children 6 months to 4 years old.

ADVERSE DRUG REACTIONS

GENERAL

  • Overall, the Pfizer-BioNTech 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 Pfizer-BioNTech COVID-19 vaccine to individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any Pfizer-BioNTech COVID-19 vaccine component.

IMMUNE RESPONSE

  • The highest neutralization titers were obtained on day 28 and day 35, confirming the need for two-dose series. Dose #2 elicited a robust immune response.
  • Geometric mean titers (GMT) on day 28 or day 35 ranged from 1.7 to 4.6 times the GMT of convalescent serum in those aged 18 - 55 years and 1.1 to 2.2 times the GMT in those aged 65 - 85 years.
  • 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

  • A multinational, placebo-controlled, observer-blinded safety and efficacy trial in individuals ≥ 16 years of age were randomized 1:1 to receive 2 doses, 21 days apart, of either placebo or the BNT162b2 vaccine.
    • The primary endpoints were vaccine efficacy against COVID-19 and safety.
    • Preliminary data that granted the December 2020 EUA suggested 95% vaccine efficacy.
    • The full six-month data of the clinical trial (NEJM 2021) had the following results, tempered by conducting the trial during the earlier phase of the pandemic (pre-Delta variant)
      • 44,165 patients received either BNT162b2 or placebo injections, ages ≥ 16 yrs, and 2264 ages 12-15 years.
        • Vaccine efficacy: 91.3% (95% confidence interval [CI], 89.0 to 93.2) in participants without evidence of previous SARS-CoV-2.
        • Vaccine efficacy was noted to decline over time.
        • Vaccine efficacy was noted to be similar across countries and subgroups, including age, sex, race, ethnicity and baseline body mass index (86-100%)
      • 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.
  • A clinical trial evaluating the vaccine in children 6 months to 11 years was initiated in March 2021; children as young as 5 years of age can receive the initial 2-dose series under the FDA EUA.
  • 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) 2 weeks after receiving booster doses.

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 Pfizer-BioNTech COVID-19 Vaccine.
  • Frozen vials MUST be stored in ultra-low-temperature freezers. Once thawed, stability is limited.
  • 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.
  • Full-dose vaccine (0.3 mL) is recommended for individuals ≥ 12 years of age; these vials contain purple caps. A reduced dose (0.2 mL) is recommended for individuals 5 - 11 years of age; these vials contain orange caps.
  • The vaccine efficacy of the bivalent booster is unknown; EUA was given based on immunogenicity and safety in limited human trials.

Basis for recommendation

  1. https://www.fda.gov/media/144413/download (Accessed 9/19/2022)

    Comment:

    Link contains the Fact Sheet for Providers administering vaccine: Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019.

References

  1. Woodworth KR, Moulia D, Collins JP, et al. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Children Aged 5-11 Years - United States, November 2021. MMWR Morb Mortal Wkly Rep. 2021;70(45):1579-1583.  [PMID:34758012]

    Comment: ACIP recommendations on the use of the Pfizer-BioNTech COVID-19 vaccine in the use of children aged 5 - 11.The EUA was amended on 10/29/21 that children aged 5 - 11 years receive 2 doses (10 mcg/0.2 mL) 3 weeks apart.

  2. Rosenblum HG, Hadler SC, Moulia D, et al. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(32):1094-1099.  [PMID:34383735]

    Comment: ACIP update deals with the rare issues described after COVID-19 immunization including GBS and TTS after Janssen/JNJ vaccine, and myocarditis/pericarditis after mRNA vaccines.

  3. 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.

  4. 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 effectivemess against infection decreased from 91.7% to 79.8%. This evaluation provides evidence for the need for a booster dose of the vaccination.

  5. 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.

  6. Walsh EE, Frenck RW, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020.  [PMID:33053279]

    Comment: This is the phase I, placebo-controlled, observer-blinded, dose-escalation trial conducted in the United States in which participants aged 18 - 55 or 65 - 85 were randomized to receive either placebo or one of two vaccine candidates (BNT162b1 or BNT162b2). The primary endpoint was safety, and immunogenicity was the secondary outcome. Vaccine responses elicited in both groups were similar in terms of dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. The incidence of adverse effects was lower in the BNT162b2 subset, and this was chosen to move forward in the phase 2/3 study.

  7. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020.  [PMID:33301246]

    Comment: In this ongoing, multinational, placebo-controlled, observer-blinded efficacy trial, participants 16 years of age or older were randomized to receive 2 doses given 21 days apart of BNT162b2 or placebo. The primary endpoint was the efficacy of the vaccine against lab-confirmed COVID-19, as well as safety. 21,720 participants received the vaccine candidate while 21,728 received placebo. There were only 8 cases of COVID-19 disease that occured at least 7 days after the second dose of the vaccine compared to 162 cases in the group who received placebo, translating to 95% efficacy. Similar vaccine efficacy was observed across subgroups (age, sex, race, ethnicity, baseline BMI), although it should be noted that 83% of all participants were Caucasian. The incidence of adverse events was similar between groups, with the most frequently reported adverse events being injection site pain, fatigue, headache and diarrhea.

  8. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):1922-1924.  [PMID:33332292]

    Comment: MMWR report providing ACIP interim recommendations endorsing the Pfizer-BioNTech 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 21 for the prevention of COVID-19 disease in those 16 years of age and older.

  9. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals (Accessed 9/19/2022)

    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.


  10. https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-.... (Accessed 9/19/2022)

    Comment: American Academy of Pediatrics discusses 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.

  11. https://www.fda.gov/media/161327/download (accessed 9/19/2022)

    Comment:

    Emergency use authorization for the Pfizer-BioNTech BIVALENT vaccine. It is recommended for use in individuals 12 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.

  12. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-and-pfizer-biontech-covid-19-vaccines-children#(Accessed 9/19/2022)

    Comment:
    FDA approval update expanding eligibility of BNT162b2 COVID-19 vaccine to children aged 6 months to 4 years.


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Last updated: September 19, 2022