VACCINE TYPE

• Effective April 19, 2023, the original monovalent Pfizer-BioNTech COVID-19 vaccine is no longer recommended; 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 and older.
• The Pfizer-BioNTech COVID-19 vaccine is a lipid nanoparticle-formulated, nucleoside-modified RNA (mRNA) vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 spike protein.
  • Primary series: Single dose, 0.3 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 who have received one dose of the monovalent vaccine: Two doses of the bivalent vaccine should be given 3 weeks after the first monovalent vaccine, with the second 8 weeks later.
  • Individuals who have received two doses of the monovalent vaccine: A single dose of the bivalent vaccine should be given at least 8 weeks after the second dose of the monovalent vaccine.
  • Individuals who have received three doses of the monovalent vaccine: A single dose of the bivalent vaccine should be given at least 2 months after the last dose of the monovalent vaccine.
• 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, 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 resulting in hospitalization or death following administration 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 6 months - 17 years can receive only the Pfizer-BioNTech vaccine).

INDICATIONS

FORMS

PATHOGEN DIRECTED PROTECTION

• COVID-19

DOSE/ADMINISTRATION

ADVERSE DRUG REACTIONS

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 booster doses.

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 Pfizer-BioNTech COVID-19 Vaccine.
  • See https://vaers.hhs.gov/reportevent.html for instructions on reporting.
• 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, 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.
• 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 6 months to 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 4/20/2023)

   Comment:
   
   The link contains the Fact Sheet for vaccine providers: Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019.
   

References

2. 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.
   

3. 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.
   

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 effectivemess 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. 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.
   

8. 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.
   

9. 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.
   

10. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals (Accessed 5/8/2023)

    Comment: A 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.
    
    
    

11. https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-.... (Accessed 5/8/2023)

    Comment: American Academy of Pediatrics discusses the CDC confirmation of more than 220 cases of myocarditis or pericarditis in those aged 30 and younger within one 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 patients who develop acute chest pain, heart palpitations, and/or shortness of breath within 1 week of receiving their second vaccine dose.
    

12. https://www.fda.gov/vaccines-blood-biologics/coronavirus-covid-19-cber-reg... (Accessed 5/8/2023)

    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 the primary COVID vaccine series is completed or two months after receipt of a previous booster.
    

13. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-and-pfizer-biontech-covid-19-vaccines-children#(Accessed 5/8/2023)

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