The Advisory Committee on Immunization Practices' Interim Recommendations for Additional Primary and Booster Doses of COVID-19 Vaccines

United States, 2021

Sarah Mbaeyi, MD; Sara E. Oliver, MD; Jennifer P. Collins, MD; Monica Godfrey, MPH; Neela D. Goswami, MD; Stephen C. Hadler, MD; Jefferson Jones, MD; Heidi Moline, MD; Danielle Moulia, MPH; Sujan Reddy, MD; Kristine Schmit, MD; Megan Wallace, DrPH; Mary Chamberland, MD; Doug Campos-Outcalt, MD; Rebecca L. Morgan, PhD; Beth P. Bell, MD; Oliver Brooks, MD; Camille Kotton, MD; H. Keipp Talbot, MD; Grace Lee, MD; Matthew F. Daley, MD; Kathleen Dooling, MD

Disclosures

Morbidity and Mortality Weekly Report. 2021;70(44):1545-1552.

Reporting of Vaccine Adverse Events

FDA requires that immunization providers report vaccine administration errors, serious adverse events, cases of multisystem inflammatory syndrome, and cases of COVID-19 that result in hospitalization or death after administration of COVID-19 vaccine under an EUA.^[2] Adverse events that occur after receipt of any COVID-19 vaccine should be reported to the Vaccine Adverse Events Reporting System (VAERS, https://vaers.hhs.gov or 1-800-822-7967). Any person who administers or receives a COVID-19 vaccine is encouraged to report any clinically significant adverse event, whether or not it is clear that a vaccine caused the adverse event. In addition, CDC has developed a new, voluntary smartphone-based online tool (v-safe) that uses text messaging and online surveys to provide near real-time health check-ins after receipt of a COVID-19 vaccine (https://www.cdc.gov/vsafe).

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Acknowledgments
Karen Broder, Amanda Cohn, Rachel Gorwitz, Anne Hause, Ruth Link-Gelles, Lauri Markowitz, Tom Shimabukuro, Rachel Slayton, John Su, Naomi Tepper, Erin Tromble, Melinda Wharton, CDC COVID-19 Response Team. Voting members of the Advisory Committee on Immunization Practices: Kevin A. Ault, University of Kansas Medical Center; Lynn Bahta, Minnesota Department of Health; Wilbur Chen, University of Maryland School of Medicine; Sybil Cineas, Warren Alpert Medical School of Brown University; James Loehr, Cayuga Family Medicine; Sarah Long, Drexel University College of Medicine; Veronica V. McNally, Franny Strong Foundation; Katherine A. Poehling, Wake Forest School of Medicine; Pablo J. Sánchez, The Research Institute at Nationwide Children's Hospital. Members of the Advisory Committee on Immunization Practices COVID-19 Vaccines Work Group: Edward Belongia, Center for Clinical Epidemiology & Population Health, Marshfield Clinic Research Institute; Henry Bernstein, Zucker School of Medicine at Hofstra/Northwell Cohen Children's Medical Center; Dayna Bowen Matthew, George Washington University Law School; Uzo Chukwuma, Indian Health Service; Marci Drees, Society for Healthcare Epidemiology of America; Jeffrey Duchin, Infectious Diseases Society of America; Kathy Kinlaw, Center for Ethics, Emory University; Doran Fink, Food and Drug Administration; Sandra Fryhofer, American Medical Association; Jason M. Goldman, American College of Physicians; Michael Hogue, American Pharmacists Association; Denise Jamieson, American College of Obstetricians and Gynecologists; Jeffery Kelman, Centers for Medicare & Medicaid; David Kim, U.S. Department of Health and Human Services; Susan Lett, Council of State and Territorial Epidemiologists; Kendra McMillan, American Nurses Association; Kathleen Neuzil, Center for Vaccine Development and Global Health, University of Maryland School of Medicine; Sean O'Leary, American Academy of Pediatrics; Christine Oshansky, Biomedical Advanced Research and Development Authority; Stanley Perlman, Department of Microbiology and Immunology, University of Iowa; Marcus Plescia, Association of State and Territorial Health Officials; Chris Roberts, National Institutes of Health; José R. Romero, Arkansas Department of Health; William Schaffner, National Foundation for Infectious Diseases; Rob Schechter, Association of Immunization Managers; Kenneth Schmader, American Geriatrics Society; Bryan Schumacher, Department of Defense; Peter Szilagyi, University of California, Los Angeles; Jonathan Temte, American Academy of Family Physicians; Matthew Tunis, National Advisory Committee on Immunization Secretariat, Public Health Agency of Canada; Matt Zahn, National Association of County and City Health Officials; Rachel Zhang, Food and Drug Administration.

Abstract and Introduction
Reporting of Vaccine Adverse Events
References
Sidebar

Table. COVID-19 vaccines approved or authorized for emergency use by the Food and Drug Administration for persons aged ≥12 years — United States, October 2021*
COVID-19 vaccine manufacturer	Primary and additional primary doses					Booster dose^†
COVID-19 vaccine manufacturer	Age, yrs	Dose (volume)	No. of doses (interval between doses)	Additional primary dose in immunocompromised persons (interval since 2nd dose)	Interval between last primary (including additional) dose to booster dose	Dose (volume)	No. of doses
Pfizer-BioNTech (Comirnaty)	12–17	30 μg (0.3 ml)	2 (21 days)	1 (≥28 days)	NA	NA	NA
Pfizer-BioNTech (Comirnaty)	≥18^§	30 μg (0.3 ml)	2 (21 days)	1 (≥28 days)	≥6 months	30 μg (0.3 ml)	1
Moderna	≥18^§	100 μg (0.5 ml)	2 (28 days)	1 (≥28 days)	≥6 months	50 μg (0.25 ml)	1
Janssen (Johnson & Johnson)	≥18	5 × 10¹⁰ VP (0.5 ml)	1 (NA)	NA	≥2 months	5 × 10¹⁰ VP (0.5 ml)	1

Abbreviations: NA = not applicable; VP = viral particles.
*As of October 29, 2021. Food and Drug Administration package inserts or fact sheets provide updated information at https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines. Route of administration is intramuscular for the currently approved or authorized COVID-19 vaccines.
^†The Advisory Committee on Immunization Practices recommends that any of the FDA-approved or authorized COVID-19 vaccines (Pfizer-BioNTech, Moderna, or Janssen) may be used for booster vaccination, regardless of the vaccine product used for primary vaccination. When a heterologous (mix-and-match) booster dose is administered, the eligible population and dosing intervals are those of the vaccine used for primary vaccination. For example, a recipient of Janssen COVID-19 vaccine may receive a Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccine booster dose ≥2 months after their primary dose. A recipient of an mRNA COVID-19 primary series who is in a risk group recommended to receive a booster dose may receive a Pfizer-BioNTech, Moderna, or Janssen COVID-19 vaccine booster dose ≥6 months after completion of the primary series. Additional information on groups recommended for an additional primary or booster dose of COVID-19 vaccine is provided at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.
^§Minimum authorized age group; see Advisory Committee on Immunization Practices' recommendations for groups recommended to receive a booster dose.

Box 1. Timeline of COVID-19 vaccine authorizations, approvals, and vaccine recommendations — United States, December 2020–October 2021
December 2020 • FDA authorizes and ACIP recommends Pfizer-BioNTech COVID-19 vaccine as a 2-dose primary series in persons aged ≥16 years. • FDA authorizes and ACIP recommends Moderna COVID-19 vaccine as a 2-dose primary series in persons aged ≥18 years. • ACIP issues interim recommendations for allocating initial supplies of COVID-19 vaccine, starting with long-term care facility residents and health care personnel, followed by other groups at risk. February 2021 • FDA authorizes and ACIP recommends Janssen (Johnson & Johnson) COVID-19 vaccine as a single dose in persons aged ≥18 years. April 2021 • CDC and FDA recommend pausing use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS) among vaccine recipients. Ten days later, ACIP concludes that the benefits of resuming Janssen COVID-19 vaccination outweighs the risks and reaffirms its interim recommendations under FDA's Emergency Use Authorization, which includes a new warning for TTS among women aged 18–49 years. May 2021 • FDA authorizes and ACIP recommends Pfizer-BioNTech COVID-19 vaccine as a 2-dose primary series in persons aged 12–15 years. June 2021 • After reports of myocarditis among mRNA COVID-19 vaccine recipients, particularly males aged 12–29 years, ACIP concludes that the benefits of COVID-19 vaccination outweigh the risks of myocarditis after vaccination. July 2021 • After reports of Guillain-Barré syndrome (GBS) in Janssen COVID-19 vaccine recipients, ACIP reviews updated benefit-risk analyses for all COVID-19 vaccines and concludes that the benefits of vaccination outweigh the risks of GBS and TTS (Janssen COVID-19 vaccine) and myocarditis (mRNA COVID-19 vaccines). August 2021 • FDA grants full approval and ACIP revises its interim recommendation to a standard recommendation for Pfizer-BioNTech COVID-19 vaccine (Comirnaty) for persons aged ≥16 years. • FDA authorizes and ACIP recommends an additional primary dose of Pfizer-BioNTech COVID-19 (for persons aged ≥12 years) and Moderna COVID-19 vaccine (for persons aged ≥18 years) in certain immunocompromised persons ≥28 days after completion of the second dose in the initial primary series. September 2021 • FDA authorizes a single Pfizer-BioNTech COVID-19 vaccine booster dose in certain persons aged ≥18 years at increased risk for serious complications of COVID-19, including severe COVID-19, who completed a Pfizer-BioNTech COVID-19 vaccine primary series ≥6 months ago. • ACIP recommends that persons aged ≥65 years, residents aged ≥18 years in long-term care settings, and persons aged 50–64 years with certain underlying medical conditions should receive a booster dose and that persons aged 18–49 years with certain underlying medical conditions may receive a single Pfizer-BioNTech COVID-19 vaccine booster dose based on individual benefits and risks. • CDC further recommends that persons aged 18–64 years at increased risk for SARS-CoV-2 exposure and transmission because of occupational or institutional setting may receive a single Pfizer-BioNTech COVID-19 vaccine booster dose based on individual benefits and risks. This recommendation is replaced by ACIP's broader recommendation in October 2021 for COVID-19 vaccine booster doses in persons who received an mRNA primary series (described below). October 2021 • FDA authorizes a single Moderna COVID-19 vaccine booster dose (50 μg) in persons aged ≥18 years at increased risk for serious complications of COVID-19 or frequent institutional or occupational exposure to SARS-CoV-2 who completed a Moderna COVID-19 vaccine primary series ≥6 months ago. • FDA authorizes a single Janssen COVID-19 vaccine booster dose in persons aged ≥18 years who received a Janssen COVID-19 vaccine dose ≥2 months ago. • FDA authorizes that Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccines may be administered as a heterologous booster dose after completion of primary vaccination with another COVID-19 vaccine. • ACIP recommends that persons aged ≥65 years, residents aged ≥18 years in long-term care settings, and persons aged 50–64 years with certain underlying medical conditions who received an mRNA COVID-19 vaccine primary series should receive a single COVID-19 vaccine booster dose ≥6 months later; persons aged 18–49 years with certain underlying medical conditions and persons aged 18–64 years at increased risk for SARS-CoV-2 exposure and transmission because of occupational or institutional setting may receive a COVID-19 booster dose based on individual benefits and risks. This recommendation replaces the September 23, 2021, ACIP recommendation for Pfizer-BioNTech COVID-19 vaccine booster doses. • ACIP recommends that persons aged ≥18 years who received Janssen COVID-19 vaccine should receive a single COVID-19 vaccine booster dose ≥2 months later.
Abbreviations: ACIP = Advisory Committee on Immunization Practices; FDA = Food and Drug Administration.

Box 2. Interim Advisory Committee on Immunization Practices' recommendations for the use of an additional primary* or booster ^† dose of COVID-19 vaccines — United States, October 2021 ^§
Additional primary mRNA COVID-19 vaccine dose in immunocompromised persons Moderately to severely immunocompromised persons^¶ aged ≥12 years (Pfizer-BioNTech) or ≥18 years (Moderna) who completed an initial mRNA COVID-19 vaccine series should receive an additional primary mRNA vaccine dose ≥28 days after their second dose. This recommendation does not apply to immunocompromised recipients of Janssen (Johnson & Johnson) COVID-19 vaccine. COVID-19 vaccine booster dose (including heterologous [mix-and-match] booster vaccination) mRNA COVID-19 vaccine (Pfizer-BioNTech, Moderna) recipients The following recipients of an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) primary series should receive a single COVID-19 vaccine booster dose ≥6 months after completion of the primary series: • Persons aged ≥65 years • Residents aged ≥18 years in long-term care settings • Persons aged 50–64 years with certain underlying medical conditions The following recipients of an mRNA primary series may receive a COVID-19 vaccine booster dose ≥6 months after completing the primary series based on their individual benefits and risks: • Persons aged 18–49 years with certain underlying medical conditions • Persons aged 18–64 years at increased risk for SARS-CoV-2 exposure and transmission because of occupational or institutional setting Any FDA-approved or authorized COVID-19 vaccine (Pfizer-BioNTech, Moderna, or Janssen) can be used as the booster dose, at an interval of ≥6 months since primary vaccination. Janssen COVID-19 vaccine recipients** • Persons aged ≥18 years who received primary vaccination with Janssen COVID-19 vaccine should receive a single COVID-19 vaccine booster dose ≥2 months later. Any FDA-approved or -authorized COVID-19 vaccine (Pfizer-BioNTech, Moderna, or Janssen) can be used as the booster dose, at an interval of ≥2 months after the primary Janssen vaccine dose.
Additional primary dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. ^†Booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. ^§Additional information is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html. ^¶As of October 29, 2021, moderately to severely immunocompromised persons include (but are not limited to) persons with the following conditions or who receive the following treatments: 1) active treatment for solid tumor and hematologic malignancies; 2) receipt of solid-organ transplant and taking immunosuppressive therapy; 3) receipt of chimeric antigen receptor T-cell or hematopoietic cell transplant; 4) moderate or severe primary immunodeficiency; 5) advanced or untreated HIV infection; 6) active treatment with high-dose corticosteroids, alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor blockers, and other immunosuppressive or immunomodulatory biologic agents. *CDC considers persons with certain underlying medical conditions to be at increased risk for developing severe outcomes of COVID-19. An-up-to date list, and supporting evidence, is available at https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html. As of October 14, 2021, the list of underlying medical conditions includes: asthma, cancer, cerebrovascular disease, chronic kidney disease, certain types of chronic lung diseases, certain types of chronic liver disease, cystic fibrosis, diabetes mellitus (type 1 and type 2), Down syndrome, heart conditions, HIV, hypertension, immune deficiencies, certain mental health disorders (i.e., mood disorders, schizophrenia spectrum disorders), obesity (BMI ≥30 kg/m²) and overweight (BMI ≥25 kg/m², but <30 kg/m²), pregnancy and recent pregnancy, sickle cell disease, smoking (current and former), solid organ or blood stem cell transplantation, substance use disorders, thalassemia, tuberculosis, and use of corticosteroids or other immunosuppressive medications. A person with a condition that is not listed might still be at greater risk for severe illness from COVID-19 than persons of similar age who do not have the condition and should talk with their health care provider. This list is not exhaustive and should not be used to exclude persons with underlying conditions from recommended preventive measures, including booster doses of COVID-19 vaccines.