Morbidity and Mortality Weekly Report

Early Release / Vol. 70 May 14, 2021

The Advisory Committee on Immunization Practices’

Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine
in Adolescents Aged 12–15 Years — United States, May 2021
Megan Wallace, DrPH1,2; Kate R. Woodworth, MD1; Julia W. Gargano, PhD1; Heather M. Scobie, PhD1; Amy E. Blain, MPH1;
Danielle Moulia, MPH1; Mary Chamberland, MD1; Nicole Reisman, MPH1; Stephen C. Hadler, MD1; Jessica R. MacNeil, MPH1;
Doug Campos-Outcalt, MD3; Rebecca L. Morgan, PhD4; Matthew F. Daley, MD5; José R. Romero, MD6; H. Keipp Talbot, MD7;
Grace M. Lee, MD8; Beth P. Bell, MD9; Sara E. Oliver, MD1

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (GRADE) approach.¶ The ACIP recommendation for the use
is a lipid nanoparticle–formulated, nucleoside-modified of the Pfizer-BioNTech COVID-19 vaccine in persons aged
mRNA vaccine encoding the prefusion spike glycoprotein of ≥12 years under an EUA is interim and will be updated as
SARS-CoV-2, the virus that causes COVID-19. Vaccination additional information becomes available.
with the Pfizer-BioNTech COVID-19 vaccine consists of Since June 2020, ACIP has convened 14 public meetings
2 intramuscular doses (30 μg, 0.3 mL each) administered to review data on the epidemiology of COVID-19 and the
3 weeks apart. On December 11, 2020, the Food and Drug potential use of COVID-19 vaccines, including the Pfizer-
Administration (FDA) issued an Emergency Use Authorization BioNTech COVID-19 vaccine (3). The ACIP COVID-19
(EUA) for use of the Pfizer-BioNTech COVID-19 vaccine Vaccines Work Group, comprising experts in infectious
(Pfizer, Inc; Philadelphia, Pennsylvania) in persons aged diseases, vaccinology, vaccine safety, public health, and ethics,
≥16 years (1); on December 12, 2020, the Advisory Committee has held weekly meetings to review COVID-19 surveillance
on Immunization Practices (ACIP) issued an interim recom- data, evidence for vaccine efficacy and safety, and implementa-
mendation for use of the vaccine in the same age group (2). tion considerations for COVID-19 vaccines. Within the EtR
As of May 12, 2021, approximately 141.6 million doses of the Framework for the Pfizer-BioNTech COVID-19 vaccine for
Pfizer-BioNTech COVID-19 vaccine had been administered adolescents aged 12–15 years, ACIP considered the importance
to persons aged ≥16 years.* On May 10, 2021, FDA expanded of COVID-19 as a public health problem, as well as issues of
the EUA for the Pfizer-BioNTech COVID-19 vaccine to resource use, benefits and harms, patients’ and parents’ values
include adolescents aged 12–15 years (1). On May 12, 2021, and preferences, acceptability, feasibility, and equity for use of
ACIP issued an interim recommendation† for use of the the vaccine among adolescents. After a systematic review of
Pfizer-BioNTech COVID-19 vaccine in adolescents aged published and unpublished evidence for benefits and harms,
12–15 years for the prevention of COVID-19. To guide its the Work Group used the GRADE approach to assess the
deliberations regarding the vaccine, ACIP used the Evidence certainty of evidence for outcomes related to the vaccine,
to Recommendation (EtR) Framework,§ using the Grading of rated on a scale of 1 (high certainty) to 4 (very low certainty)
Recommendations, Assessment, Development and Evaluation (4). Work Group conclusions regarding the evidence for the
Pfizer-BioNTech COVID-19 vaccine were presented to ACIP
* Accessed May 12, 2021. https://covid.cdc.gov/covid-data-tracker/#vaccinations
† On May 12, 2021, ACIP voted 14–0 (one recusal) in favor of the interim at a public meeting on May 12, 2021.
recommendation for use of Pfizer BioNTech COVID-19 vaccine for persons The body of evidence for the Pfizer-BioNTech COVID-19
aged 12–15 years. One ACIP member recused herself because of participation vaccine was primarily guided by one randomized, double-blind,
in clinical trials and other studies involving companies producing
COVID-19 vaccines. placebo-controlled Phase II/III clinical trial that was expanded
§ https://www.cdc.gov/vaccines/acip/recs/grade/downloads/ACIP-evidence-rec-
¶ https://www.cdc.gov/vaccines/acip/recs/grade/about-grade.html
frame-508.pdf

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention
 Early Release

to enroll approximately 2,200 participants aged 12–15 years, safety data, including information on reactogenicity, is available
randomized 1:1 to receive vaccine or saline placebo (5). at https://www.cdc.gov/vaccines/covid-19/info-by-product/
Interim findings from this clinical trial were based on data pfizer/reactogenicity.html.
from participants with a median of 2 months of follow-up. The From the GRADE evidence assessment, the level of certainty
estimated efficacy of the Pfizer-BioNTech COVID-19 vaccine for the benefits of Pfizer-BioNTech COVID-19 vaccination
was supported by two types of evidence: clinical efficacy and among adolescents aged 12–15 years was type 1 (high certainty)
immunobridging. In the direct clinical assessment, efficacy for the prevention of symptomatic COVID-19. Regarding
was 100% (95% confidence interval [CI] = 75.3%–100%) in potential harms after vaccination, evidence was type 4
preventing symptomatic, laboratory-confirmed COVID-19 (very low certainty) for serious adverse events and type 1
in adolescents aged 12–15 years without evidence of previous (high certainty) for reactogenicity. No data were available to
SARS-CoV-2 infection. Vaccine efficacy was also supported by assess the other GRADE benefits and harms including pre-
immunobridging data from vaccine recipients aged 12–15 years vention of hospitalization due to COVID-19, prevention of
compared with those from recipients aged 16–25 years. multisystem inflammatory syndrome in children (MIS-C),
The immune response to 2 doses of the Pfizer-BioNTech SARS-CoV-2 seroconversion to a nonspike protein, or preven-
COVID-19 vaccine in adolescents aged 12–15 years without tion of asymptomatic SARS-CoV-2 infection.
evidence of previous SARS-CoV-2 infection was at least as Data reviewed within the EtR Framework supported the
high as the response observed in persons aged 16–25 years; use of the Pfizer-BioNTech COVID-19 vaccine in adoles-
the geometric mean ratio for 50% neutralizing antibody titer cents aged 12–15 years. ACIP determined that COVID-19
was 1.76 (95% CI  =  1.47–2.10), demonstrating statistical in adolescents is a major public health problem. Adolescents
noninferiority.** Among adolescent vaccine recipients aged represent a growing proportion of new COVID-19 cases
12–15 years, reactogenicity symptoms, defined as solicited local reported to CDC§§ and have been shown to contribute to
injection site or systemic reactions during the 7 days after vac- household transmission (6). As of May 1, 2021, the cumula-
cination, were frequent (90.9% of vaccine recipients reported tive COVID-19–associated hospitalization rate for adolescents
any local reaction, and 90.7% reported any systemic reaction) aged 12–17 years was 51.3 per 100,000 population,¶¶ which
and mostly mild to moderate. Systemic adverse reactions were is higher than the influenza-associated hospitalization rate
more commonly reported after the second dose than after the for the same age group during the 2009 H1N1 influenza
first dose, had a median onset of 1–4 days after vaccine receipt, pandemic (23.9 per 100,000 population).*** As of May 3,
and resolved in a median of 1–2 days. Severe local and systemic 2021, CDC had received reports of 3,742 cases of MIS-C, a
adverse reactions (grade ≥3, defined as interfering with daily severe hyperinflammatory syndrome occurring several weeks
activity) occurred more commonly in vaccine recipients than in after acute SARS-CoV-2 infection; 21.5% of the MIS-C
placebo recipients. Among vaccine recipients, 10.7% reported cases have occurred in adolescents aged 12–17 years.††† ACIP
any reaction of grade ≥3; the most common symptoms were determined that use of the Pfizer-BioNTech COVID-19 vac-
fatigue (3.5%), fever (3.0%), headache (2.7%), chills (2.1%), cine among adolescents is a reasonable and efficient allocation
and injection-site pain (1.5%). Overall, reactions of grade ≥3 of resources. Whereas there might be uncertainty regarding
were also more commonly reported after the second dose than how different populations value the vaccine, results from
after the first dose. The frequency of serious adverse events†† several surveys suggest that approximately one half of parents
was low among all participants; five serious adverse events were willing to have their adolescent children vaccinated
(0.4%) were reported among vaccine recipients and two (0.2%) (range = 46%–60%).§§§ Overall, ACIP determined that the
among placebo recipients, with no statistically significant dif- desirable effects clearly outweighed any undesirable effects in
ference in frequency observed between the two groups (5). most settings. In expanding COVID-19 vaccine access, addi-
These serious adverse events encompassed medical events tional considerations should be given to demographic groups
occurring at a frequency similar to that in the general popula- with disproportionate COVID-19 morbidity and mortality,
tion aged 12–15 years, with none considered to be related to as well as those with barriers to routine health care (e.g.,
vaccination (5). No specific safety concerns were identified adolescents of certain racial/ethnic groups and those living in
among adolescent vaccine recipients. A detailed summary of a rural or frontier area, experiencing homelessness, having a
** 1.5-fold noninferiority criterion: lower bound of the two-sided 95% CI §§ https://covid.cdc.gov/covid-data-tracker/#demographicsovertime
for geometric mean ratio >0.67. ¶¶ https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html
†† Serious adverse events are defined as any untoward medical occurrence that *** https://gis.cdc.gov/GRASP/Fluview/FluHospRates.html
results in death, is life-threatening, requires inpatient hospitalization or ††† https://www.cdc.gov/mis-c/cases/index.html
prolongation of existing hospitalization, or results in persistent §§§ https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer-biontech-etr-
disability/incapacity. 12-15-years.html

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disability, or lacking health insurance). Providing rapid and

Summary
equitable access to COVID-19 vaccine for adolescents will
What is already known about this topic?
require a stepwise approach, including augmenting existing
infrastructure for vaccination, increasing enrollment of pro- On May 10, 2021, the Food and Drug Administration
expanded Emergency Use Authorization for the Pfizer-BioNTech
viders caring for adolescents into the COVID-19 vaccination COVID-19 vaccine to include adolescents aged 12–15 years.
program, and applying school-focused strategies to ensure vac-
What is added by this report?
cination opportunities for a diverse population. Some aspects
On May 12, 2021, after a systematic review of all
of the Pfizer-BioNTech COVID-19 vaccine (e.g., cold-chain
available data, the Advisory Committee on Immunization
storage requirements or large minimum order sizes) might Practices made an interim recommendation for use of the
limit access to the vaccine among some populations, which Pfizer-BioNTech COVID-19 vaccine in adolescents aged
could negatively affect health equity. Advancing health equity, 12–15 years for the prevention of COVID-19.
particularly in populations that experience disproportionate What are the implications for public health practice?
COVID-19 morbidity and mortality, requires engagement The Pfizer-BioNTech COVID-19 vaccine is the first COVID-19
with community leaders, adolescent health care providers, and vaccine approved for use in adolescents and has high efficacy
parents to identify and remove barriers to COVID-19 vacci- against symptomatic COVID-19. Vaccination will be important
nation, including those related to vaccine access and vaccine to protect adolescents against symptomatic COVID-19 disease
and to reduce community transmission of SARS-CoV-2.
confidence. The GRADE evidence profile and EtR supporting
evidence are available at https://www.cdc.gov/vaccines/acip/
recs/grade/covid-19-pfizer-biontech-vaccine-12-15-years.html
and https://www.cdc.gov/vaccines/acip/recs/grade/covid-19- COVID-19 vaccine is encouraged to report any clinically sig-
pfizer-biontech-etr-12-15-years.html. nificant adverse event, whether or not it is clear that a vaccine
Before vaccination, the EUA Fact Sheet should be provided caused the adverse event. In addition, CDC has developed
to recipients and parents or guardians. There is no federal, legal a new, voluntary smartphone-based online tool (v-safe) that
requirement for caregiver consent for COVID-19 vaccination uses text messaging and online surveys to provide near real-
or any other vaccination; however, COVID-19 vaccine must time health check-ins after receipt of a COVID-19 vaccine.
be administered according to applicable state and territorial Parents or guardians can register their adolescent children in
vaccination laws. Providers should counsel Pfizer-BioNTech v-safe and complete the health surveys on their behalf. CDC’s
COVID-19 vaccine recipients and parents or guardians about v-safe call center follows up on reports to v-safe that include
expected systemic and local reactogenicity. Additional clinical possible medically significant health events to collect additional
considerations are available at https://www.cdc.gov/vaccines/ information for completion of a VAERS report. Information
covid-19/info-by-manufacturer/pfizer/clinical-considerations. on v-safe is available at https://www.cdc.gov/vsafe.
html. The interim recommendation and clinical considerations Acknowledgments
are based on use of the Pfizer-BioNTech COVID-19 vaccine
Voting members of the Advisory Committee on Immunization
under an EUA and might change as more evidence becomes
Practices: Kevin A. Ault, University of Kansas Medical Center; Lynn
available. ACIP will continue to review additional data as they Bahta, Minnesota Department of Health; Henry Bernstein, Zucker
become available; updates to recommendations or clinical con- School of Medicine at Hofstra/Northwell Cohen Children’s Medical
siderations will be posted on the ACIP website (https://www. Center; Wilbur Chen, University of Maryland School of Medicine;
cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html). Matthew Daley, Institute for Health Research, Kaiser Permanente
Colorado; Sharon E. Frey, Saint Louis University Medical School;
Reporting of Vaccine Adverse Events Camille Kotton, Harvard Medical School; Sarah Long, Drexel
FDA requires that vaccination providers report vaccination University College of Medicine; Veronica V. McNally, Franny
administration errors, serious adverse events, cases of mul- Strong Foundation; Katherine A. Poehling, Wake Forest School of
tisystem inflammatory syndrome, and cases of COVID-19 Medicine; Pablo J. Sánchez, The Research Institute at Nationwide
Children’s Hospital. Members of the Advisory Committee on
that result in hospitalization or death after administration
Immunization Practices COVID-19 Vaccines Work Group: Edward
of COVID-19 vaccine under an EUA (7). Adverse events Belongia, Center for Clinical Epidemiology & Population Health,
that occur after receipt of any COVID-19 vaccine should Marshfield Clinic Research Institute; Dayna Bowen Matthew,
be reported to the Vaccine Adverse Events Reporting George Washington University Law School; Oliver Brooks, National
System (VAERS). Information on how to submit a report Medical Association; Jillian Doss-Walker, Indian Health Service;
to VAERS is available at https://vaers.hhs.gov/index.html or Marci Drees, Society for Healthcare Epidemiology of America; Jeffrey
1-800-822-7967. Any person who administers or receives a Duchin, Infectious Diseases Society of America; Kathy Kinlaw,

MMWR  /  May 14, 2021  /  Vol. 70 3

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Center for Ethics, Emory University; Doran Fink, Food and Drug References
Administration; Sandra Fryhofer, American Medical Association; 1. Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine
Jason M. Goldman, American College of Physicians; Michael Hogue, emergency use authorization. Silver Spring, MD: US Department of
American Pharmacists Association; Denise Jamieson, American Health and Human Services, Food and Drug Administration; 2021.
College of Obstetricians and Gynecologists; Jeffery Kelman, Centers https://www.fda.gov/emergency-preparedness-and-response/coronavirus-
disease-2019-covid-19/pfizer-biontech-covid-19-vaccine
for Medicare & Medicaid; David Kim, U.S. Department of Health 2. Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on
and Human Services; Susan Lett, Council of State and Territorial Immunization Practices’ interim recommendation for use of Pfizer-
Epidemiologists; Kendra McMillan, American Nurses Association; BioNTech COVID-19 vaccine—United States, December 2020. MMWR
Kathleen Neuzil, Center for Vaccine Development and Global Morb Mortal Wkly Rep 2020;69:1922–4. PMID:33332292 https://doi.
Health, University of Maryland School of Medicine; Sean O’Leary, org/10.15585/mmwr.mm6950e2
3. Advisory Committee on Immunization Practices. ACIP meeting
American Academy of Pediatrics; Christine Oshansky, Biomedical information. Atlanta, GA: US Department of Health and Human Services,
Advanced Research and Development Authority; Stanley Perlman, CDC; 2021. https://www.cdc.gov/vaccines/acip/meetings/index.html
Department of Microbiology and Immunology, University of Iowa; 4. Advisory Committee on Immunization Practices. Advisory Committee
Marcus Plescia, Association of State and Territorial Health Officials; on Immunization Practices (ACIP): GRADE (grading of recommendations,
Chris Roberts, National Institutes of Health; William Schaffner, assessment, development and evaluation). Atlanta, GA: US Department
of Health and Human Services, CDC; 2020. https://www.cdc.gov/
National Foundation for Infectious Diseases; Kenneth Schmader, vaccines/acip/recs/grade
American Geriatrics Society; Bryan Schumacher, Department of 5. Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine.
Defense; Rob Schechter, Association of Immunization Managers; EUA amendment review memorandum. Silver Spring, MD: US
Jonathan Temte, American Academy of Family Physicians; Peter Department of Health and Human Services, Food and Drug
Szilagyi, University of California, Los Angeles; Matthew Tunis, Administration; 2021. https://www.fda.gov/media/148542/download
6. Lessler J, Grabowski MK, Grantz KH, et al. Household COVID-19 risk
National Advisory Committee on Immunization Secretariat, Public and in-person schooling. Science 2021. Epub April 29, 2021.
Health Agency of Canada; Thomas Weiser, Indian Health Service; PMID:33927057 https://doi.org/10.1126/science.abh2939
Matt Zahn, National Association of County and City Health 7. Food and Drug Administration. Fact sheet for healthcare providers
Officials; Rachel Zhang, Food and Drug Administration. administering vaccine (vaccination providers). Emergency use
authorization (EUA) of the Janssen COVID-19 vaccine to prevent
Corresponding author: Sara E. Oliver, yxo4@cdc.gov.
coronavirus disease 2019 (COVID-19). Silver Spring, MD: US
1CDC COVID-19 Response Team; 2Epidemic Intelligence Service, CDC; Department of Health and Human Services, Food and Drug
3University of Arizona, College of Medicine, Phoenix, Arizona; 4Department Administration; 2021. https://www.fda.gov/media/146304/download
of Health Research Methods, Evidence and Impact, Hamilton, Ontario;
5Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado;
6Arkansas Department of Health; 7Vanderbilt University School of Medicine,
Nashville, Tennessee; 8Stanford University School of Medicine, Stanford,
California; 9University of Washington, Seattle, Washington.
All authors have completed and submitted the International
Committee of Medical Journal Editors form for disclosure of
potential conflicts of interest. No potential conflicts of interest
were disclosed.

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