cdc.gov/coronavirus

Evidence to Recommendations Framework: 

Bivalent COVID-19 Vaccine Booster Doses

Sara Oliver, MD, MSPH

ACIP Meeting

September 1, 2022
Evidence to Recommendations Framework
▪ Structure to describe information considered in moving from evidence to 

ACIP vaccine recommendations

▪ Provide transparency around the impact of additional factors on 

deliberations when considering a recommendation 

Evidence to Recommendations (EtR) Framework

3
Evidence to Recommendations (EtR) Framework 

EtR Domain Question(s)

Public Health Problem • Is the problem of public health importance?

Benefits and Harms

• How substantial are the desirable anticipated effects?

• How substantial are the undesirable anticipated effects?

• Do the desirable effects outweigh the undesirable effects?

Values

• Does the target population feel the desirable effects are large relative to 

the undesirable effects?

• Is there important variability in how patients value the outcome?

Acceptability • Is the intervention acceptable to key stakeholders?

Feasibility • Is the intervention feasible to implement?

Resource Use • Is the intervention a reasonable and efficient allocation of resources?

Equity • What would be the impact of the intervention on health equity?

4
▪ In April – August 2022, a subset of the COVID-19 ACIP Work Group engaged in a 

critical review of the Equity Domain and gathered extensive input and feedback on 

strategies to adjust the domain through the following mechanisms:

– A thorough review of use of the Equity Domain (April 2022)

– A one-time consultation with health equity experts (May 2022)

– An iterative review of possible adjustment strategies with experts (June—August 2022)

– Presentation to leadership and membership of the National Medical Association (August 2022)

– Presentation to the Structural & Social Determinants of Health Workgroup of the Office of Minority Health and 

Health Equity (August 2022) 

– Throughout this process, it became clear that consideration of equity is integral to every aspect of production, 

study, authorization and recommendation of COVID-19 vaccines 

Soliciting feedback on the Equity Domain adjustment

5
▪ The need for a systematic, reliable, and action-oriented review of evidence toward 

enhanced equity was made clear: structural problems require structural solutions

– Adjustment of structure is required for meaningful change 

– Adjustment of the EtR Framework to enable systematic and reliable review of evidence toward actionable 

recommendations to enhance equity may facilitate meaningful change

▪ We recommend restructuring the Equity Domain as a consideration across each EtR Domain:

Restructuring the Equity Domain of the Evidence to 

Recommendations (EtR) Framework 

6
Evidence to Recommendations (EtR) Framework

“The intervention” = Bivalent COVID-19 vaccine booster doses

“The problem” = COVID-19 7
▪ Does ACIP support the use of updated (bivalent) COVID-19 vaccine booster 

doses, for those individuals in age groups currently recommended to receive 

a COVID-19 vaccine booster? 

Evidence to Recommendations (EtR) Framework

Question

8
▪ Does ACIP support the use of updated (bivalent) COVID-19 vaccine booster doses, for those 

populations currently recommended to receive a COVID-19 vaccine booster? 

Evidence to Recommendations (EtR) Framework

Question

9

Dose 1

(primary)

Dose 2 

(primary)

Dose 3

(booster)

People ages 5-49 years

Dose 1

(primary)

Dose 2 

(primary)

Dose 3

(booster)

People ages 50 years and older

Primary 

Dose

Primary 

Dose

Bivalent 

Booster

Dose 4

(booster)

People ages 5 years and older*

Current recommendations Future proposed recommendations

*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC

Regardless of previous booster doses given
EtR Domain: Public Health Problem
CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailycases Accessed August 30, 2022

Daily Trends in Reported COVID-19 Cases, United States

11

Alpha Delta

Omicron

As of August 29, 2022:

94,110,810 reported cases
Weekly Trends in COVID-19-Associated Hospitalization Rates by Age Group 

— COVID-NET, March 2020 – August 20, 2022

Source: COVID-NET; https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html Accessed August 26, 2022 12

Age Group

Alpha

Delta

Omicron

Since April, 

hospitalization

rates in older age 

increased relative 

to other age groups 
Age-Adjusted Rates of COVID-19-Associated Hospitalization by Vaccination Status 

and Receipt of Booster Dose in Adults Ages ≥18 Years, January 2021–June 2022

CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination Accessed August 3, 2022

Alpha

Delta

Omicron

In June 2022, 

unvaccinated adults 

ages ≥18 years had 

4.6X higher 

COVID-19-associated 

hospitalization rates 

compared to those 

vaccinated with at least 

one booster dose

13
Age-Adjusted Rates of COVID-19-Associated Deaths by Vaccination Status and Receipt of 

Booster Dose,* September 19, 2021 – July 2, 2022 (29 U.S. Jurisdictions)

*This includes people who received booster doses and people who received additional doses. Vertical lines denote changes in booster dose recommendations.

CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Accessed August 24, 2022 

14

In June 2022, 

unvaccinated people 

ages ≥5 years had 

8X higher 

COVID-19-associated 

death rates compared 

to those with at least 

one booster dose

This was a decrease 

from ~20X during

January-March 2022

Delta

Omicron
Death Rates by Vaccination Status and Receipt of 1st and 2nd Booster Doses Among 

People Ages 50+ Years

April 3–July 2, 2022 (25 U.S. Jurisdictions)

*Includes either a booster or additional dose. 

https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccinbooine-status. Accessed August 24, 2022

In June 2022, people ages 

50 years and older with 

≥2 booster doses had 

14 times lower risk of dying 

from COVID-19, compared 

to unvaccinated people and 

3 times lower risk of dying 

from COVID-19 than people

with one booster dose

15
Percent of population with a completed COVID-19 primary 

series – United States, January 2020 – August 2022

Source: CDC Immunization Data Lake. Accessed 8/22/22

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Ages 5-11 Population % Ages 12-17 Population % Ages 18-49 Population % Ages 50-64 Population % Ages 65+ Population %

92%

82%

69%

60%

30%

16
Percent of population with a completed COVID-19 first booster 

– United States, September 2021 – August 2022

Source: CDC Immunization Data Lake. Accessed 8/22/22; First boosters does not include Texas for all ages or Idaho for ages <18

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

09/11/21 10/11/21 11/11/21 12/11/21 01/11/22 02/11/22 03/11/22 04/11/22 05/11/22 06/11/22 07/11/22 08/11/22

Ages 5-11 Population % Ages 12-17 Population % Ages 18-49 Population % Ages 50-64 Population % Ages 65+ Population %

69%

55%

40%

30%

13%

17
Percent of population with a completed COVID-19 second 

booster – United States, September 2021 – August 2022

Source: CDC Immunization Data Lake. Accessed 8/22/22; Second boosters does not include Texas for all ages or Idaho for ages <18

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Ages 50-64 Population % Ages 65+ Population %

41%

25%

18
Domain Equity Question:

Does the problem impact all populations equally?

19
COVID-19 case and death rates in the United States, 

by county urban/rural classification 

CDC COVID Data Tracker. Trends in COVID-19 Cases and Deaths in the United States, by County-level Population Factors. https://covid.cdc.gov/covid-data-tracker/#popfactors_7daynewcases Accessed August 25, 2022 20

▪ In the recent Omicron surge, the case rate (left) was higher among a large metro 

classification, while death rate (right) was higher in rural populations

Case rate per 100,000 population Death rate per 100,000 population
COVID-19 weekly cases per 100,000 population by race and 

ethnicity, United States, March 1, 2020 – August 27, 2022*

CDC COVID Data Tracker. COVID-19 Weekly Cases and Deaths per 100,000 Population by Age, Race/Ethnicity, and Sex. https://covid.cdc.gov/covid-datatracker/#demographicsovertime Accessed August 25, 2022 21
Characteristics of COVID-19-associated hospitalizations by race 

and ethnicity, March 1, 2020 – June 30, 2022

CDC COVID Data Tracker. COVID-NET Laboratory-confirmed COVID-19 hospitalizations. https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalization-network Accessed 

August 25, 2022 22
Weekly Trends in Age-Adjusted COVID-19 Mortality Rates by Race/Ethnicity, 

United States, March 1, 2020 – August 20, 2022

Provisional Death Certificate Data, National Vital Statistics System

Source: https://data.cdc.gov/NCHS/Provisional-Weekly-Deaths-by-Region-Race-Age/tpcp-uiv5 (National Vital Statistics System provisional death certificate data) 23

0

2

4

6

8

10

12

14

16

18

Mar-20 Jun-20 Sep-20 Dec-20 Mar-21 Jun-21 Sep-21 Dec-21 Mar-22 Jun-22

Age Adjusted Deaths per 100,000

Week of Death

American Indian/Alaska Native Asian/Pacific Islander Black Hispanic/Latino White

Recent mortality rates 

show less evidence of 

disparities
▪ As of August 2022, over 94 million COVID-19 cases reported in the United States

▪ Since April 2022, hospitalization rates in older age groups increased relative to other 

age groups

– Moreover, in June 2022, during Omicron predominance, unvaccinated adults ages 18 years and older had 4.6X 

higher COVID-19-associated hospitalization rates compared to those vaccinated with at least one booster dose

▪ In June 2022, unvaccinated people ages ≥5 years had 8X higher COVID-19-associated 

death rates compared to those with at least one booster dose

– Additionally, people ages 50 years and older with ≥2 booster doses had 14X lower risk of dying from 

COVID-19, compared to unvaccinated people and 3X lower risk of dying from COVID-19 than people 

with one booster dose

▪ Vaccination rates are much higher among older adults relative to other age groups

▪ People of racial and ethnic minority groups have been disproportionately burdened 

by COVID-19 illness, hospitalization, and death

Summary

Public Health Problem

24
Public Health Problem

Work Group Interpretation

Is COVID-19 disease among populations currently recommended 

for a booster of public health importance?

oNo oProbably no oProbably yes oYes oVaries oDon’t know
EtR Domain: Benefits and Harms
▪ Clinical trial data from COVID-19 vaccine manufacturers 

– Moderna bivalent booster clinical trial 

– Pfizer-BioNTech bivalent booster clinical trial

▪ Other considerations

– Myocarditis/pericarditis 

– Modeling data

– Immune tolerance

– Imprinting

– Antigenic cartography

– BA.1 and BA.4/BA.5

– Prior SARS-CoV-2 infection 

– Non mRNA COVID-19 vaccines 

Summary of available data

27
▪ Moderna bivalent booster clinical trial with BA.1 

–mRNA-1273.214: 50 μg bivalent: 25 μg ancestral + 25 μg BA.1

▪ Pfizer-BioNTech bivalent booster clinical trial with BA.1 

–BNT162b2+BNT162b2 Omi: 30 μg bivalent: 15 μg ancestral + 15 μg BA.1 

▪ No international data yet available for bivalent boosters

▪ No clinical trial data for bivalent boosters with BA.4/5 available to date

Summary of available clinical trial data

28
▪ Moderna Phase 2/3 trial, 50 μg bivalent vaccine (mRNA-1273.214)

▪ 25 μg each ancestral Wuhan-Hu-1 and Omicron B.1.1.529 spike as a second booster 

vaccine (P205 Part G) compared to 50 μg mRNA 1273 (ancestral) as a second booster 

vaccine (P205 Part F)

▪ Population: Adults aged ≥18 years (Study 205)

– 437 participants received mRNA-1273.214 (bivalent)

– 377 received mRNA-1273 booster (ancestral)

▪ Dosing interval from first booster to bivalent booster was 136 days and from first booster 

to second ancestral booster was 134 days

▪ Median follow up 

– Bivalent booster dose: 43 days

– Ancestral booster dose: 57 days

Evidence: Moderna

29
Immunogenicity: Moderna bivalent booster

https://www.medrxiv.org/content/10.1101/2022.06.24.22276703v1.full.pdf

Assay Timepoint Bivalent mRNA-1273.214

GMT (95% CI)

mRNA-1273

GMT (95% CI)

Vaccine group/mRNA-1273 

GMR

Without evidence of prior infection N=334 N=260

Omicron neutralizing 

antibody (ID50) Day 29 postdose

2372.4 

(2070.6, 2718.2)

1473.5 

(1270.8, 1708.4)

1.75 

(1.49, 2.04)

Ancestral SARS-CoV-2

neutralizing antibody (ID50)

5977.3

(5321.9, 6713.3)

5649.3

(5056.8, 6311.2)

1.22

(1.08,1.37)

With or without evidence of prior infection N=428 N=367

Omicron neutralizing 

antibody (ID50)

Day 29 postdose

3070.4 

(2685.4, 3510.6)

1932.8

(1681.2, 2222.0)

1.78

(1.56, 2.04)

Ancestral SARS-CoV-2 

neutralizing antibody (ID50)

6619.0

(5941.7, 7373.5)

6048.5

(5465.9, 6691.0)

1.24

(1.12, 3.36)

▪ Participants ≥18 years on day 29 after the study vaccination

▪ Bivalent vaccine met superiority* criteria for both Omicron and ancestral SARS-CoV-2 antibodies 

30

GMR= geometric mean ratio; GMT= geometric mean titer; ID50 = 50% inhibitory dilution

*Superiority criterion: the lower bound of the 95% CI for GMR is >1.0
Immunogenicity: Moderna bivalent booster

https://www.medrxiv.org/content/10.1101/2022.06.24.22276703v1.full.pdf

▪ Met superiority criteria* in participants ≥18 years with or without evidence of infection 

on day 29

*Superiority criterion: the lower bound of the 95% CI for GMR is >1.0 31
▪ Local reactogenicity from Moderna bivalent booster (mRNA-1273.214) as a 4th dose 

similar to reactogenicity from 2nd dose of primary series and 3rd dose of mRNA-1273

▪ Systemic adverse reactions from Moderna bivalent booster (mRNA-1273.214) as a 

4

th dose lower than systemic reactions from 2nd dose of primary series and 3rd dose 

of mRNA-1273

▪ Fifteen participants (3.4%) had a Grade 3 local reaction and the most commonly 

reported was redness (2.1%)

▪ Twenty-four participants (5.5%) had a Grade 3 systemic reaction and the most 

commonly reported was fatigue (3.4%)

▪ No Grade 4 solicited systemic reactions were reported

Reactogenicity: Moderna bivalent booster

32
0

10

20

30

40

50

60

70

80

90

Pain Axillary

swelling or

tenderness

Erythema

(redness)

Swelling

(hardness)

Percent of participants reporting reaction

Local and systemic reactogenicity: Moderna bivalent booster

33

0

10

20

30

40

50

60

70

80

90

Percent of participants reporting reaction
▪ No serious adverse events were assessed as related to vaccine

▪ 2 participants each experienced two serious adverse events: prostate cancer diagnosis 

and traumatic fracture within 28 days of the booster dose

▪ There were no deaths or adverse events of special interest, including myocarditis or 

pericarditis

▪ In the bivalent booster group, all severe events included reactogenicity events (fatigue, 

chills, arthralgia, headache); one participant reported lymphadenopathy 

(axillary/cervical)

Serious adverse events: Moderna bivalent booster

34
▪ Pfizer-BioNTech bivalent booster clinical trial with BA.1 (C4591031) 

– Fourth dose of 30 μg bivalent [BNT162b2 (ancestral)+BNT162b2 Omi (BA.1)] compared 

with fourth dose of 30 μg BNT162b2 (monovalent)

• Substudy E evaluated safety and immunogenicity among participants ages >55 years

› Population: 305 participants received bivalent BNT162b2 Omi (BA.1) and 305 

received monovalent BNT162b2 

› Dosing interval from first booster to second booster was 6.3 months

› Median follow-up after second booster 1.7 to 1.8 months

Evidence: Pfizer

35
Immunogenicity: Pfizer bivalent booster, ages >55 years

Vaccines and Related Biological Products Advisory Committee June 28, 2022 Meeting Presentation- Pfizer/BioNTech COVID-19 Omicron-Modified Vaccine Options (fda.gov)

Assay Timepoint Bivalent Vaccine

OMI 30μg

GMT (95% CI)

BNT162b2 30μg

GMT (95%)

Vaccine group/BNT162b2 

30μg

GMR (95% CI)

N=178 N=163

SARS-CoV-2 

neutralization 

assay—Omicron 

BA.1—NT50 (titer)

1 month 

post-dose

711.0 

(588.3, 859.2) 

455.8

(365.9, 567.6)

1.56 

(1.17, 2.08)

N=186 N=182

SARS-CoV-2 

neutralization 

assay—Reference 

strain—NT50 (titer)

1 month 

post-dose

5933.2 

(5188.2, 6785.2)

5998.1

(5223.6, 6887.4)

0.99 

(0.82, 1.20)

▪ Superiority* criterion met against Omicron BA.1 and non-inferiority criterion met against reference 

strain

*simple superiority criterion: the lower bound of the 95% CI for GMR is >1.0; non-inferiority criterion: the lower bound of the 95% CI for GMR is >0.67 

36
▪ Safety population Study D, n=640

▪ Bivalent Omicron-modified vaccine (30-μg) showed similar local and systemic event 

profile as the prototype vaccine among participants age >55 years

– Fever >38.9 °C to 40.0 °C was reported by 4 participants in the vaccine group. No 

fevers >40.0 °C were reported. 

▪ For 18–55-year-olds, monovalent Omicron-modified vaccine (30 μg dose) showed 

similar reaction as prototype vaccine. No bivalent reactogenicity data available in this 

age group.

Reactogenicity: Pfizer bivalent booster 

37
0

10

20

30

40

50

60

70

80

90

Pain at the

injection site

Swelling at the

injection site

Redness at the

injection site

Percent of participants reporting reaction

Local and systemic reactogenicity: 

Pfizer bivalent booster, ages >55 years

38

0

10

20

30

40

50

60

70

80

90

Percent of participants reporting reaction
▪ No serious adverse events were assessed as related to vaccine

▪ No life-threatening (Grade 4) adverse events, or deaths were reported by participants

▪ No cases of anaphylaxis, hypersensitivity, myocarditis, pericarditis, appendicitis, Bell’s 

palsy or rash were reported

▪ In the bivalent booster group, all severe events included reactogenicity events; 

fatigue, chills, arthralgia, headache. 

▪ Mild to moderate events of lymphadenopathy

Serious adverse events: Pfizer bivalent booster

39
Summary

Clinical trial data 

40

▪ Bivalent booster doses of both Moderna & Pfizer-BioNTech COVID-19 vaccines 

increase immune response in those who have completed a primary series and a 

previous booster

– Compared with ancestral booster dose

• Demonstrated superior response to Omicron

• Demonstrated non-inferior response to ancestral strain

▪ Similar reactogenicity profile to primary series (and ancestral booster dose)

▪ Data from clinical trial limited in size, age, and bivalent booster type
▪ Myocarditis risk following bivalent COVID-19 vaccine booster dose is unknown

▪ Limited data on 2nd booster dose of current COVID-19 vaccine (only adults ages ≥50 

years), but will review risk of myocarditis following 2

nd dose in primary series and 

1

st booster dose by age group/sex

Potential myocarditis risk following bivalent booster dose

41
VAERS reporting rates of verified myocarditis per 1 million mRNA COVID-19 

vaccinations (Pfizer-BioNTech and Moderna combined), days 0–7 postvaccination*,†

* As of August 18, 2022. Reports verified to meet case definition by provider interview or medical record review.

† An estimated 1–10 cases of myocarditis per 100,000 person years occurs among people in the United States, regardless of vaccination status; adjusted for days 0–7 

risk interval, this estimated background is 0.2 to 2.2 per 1 million person-day 0–7 risk interval (peach shaded cells indicate that reporting rate exceeded estimated 

background incidence for the period) 42

Dose 2

(primary series)

1st booster

dose

Age group Male Female Male Female

5–11 years 2.5 0.7 0.0 0.0

12–15 years 47.1 4.2 12.9 0.7

16–17 years 78.7 7.4 21.6 0.0

18–24 years 39.3 3.9 13.1 0.6

25–29 years 15.3 3.5 4.4 2.2

30–39 years 7.8 1.0 1.9 0.9

40–49 years 3.3 1.6 0.2 0.6

50–64 years 0.7 0.5 0.4 0.1

65+ years 0.3 0.5 0.7 0.2
VSD incidence rates of verified myocarditis/pericarditis in the 0–7 days 

after Pfizer-BioNTech vaccination in people ages 12–39 years, dose 2 and 

1

st booster*

43

Dose 2 primary series

Pfizer-BioNTech

1

st booster dose

Pfizer-BioNTech

Cases

Dose 2 

admin

Incidence rate/

million doses (95% CI) Cases

1

st boosters

admin

Incidence rate/

million doses (95% CI)

12–15 years

Males 31 205,955 150.5 (102.3 – 213.6) 5 81,613 61.3 (19.9 – 143.0)

Females 5 204,074 24.5 (8.0 – 57.2) 0 84,114 0.0 (0.0 – 35.6)

16–17 years

Males 14 102,091 137.1 (75.0 – 230.1) 9 47,874 188.0 (86.0 – 356.9)

Females 1 107,173 9.3 (0.2 – 52.0) 2 55,004 36.4 (4.4 – 131.3)

18–29 years

Males 27 331,889 81.4 (53.6 – 118.4) 7 166,973 41.9 (16.9 – 86.4)

Females 2 400,321 5.0 (0.6 – 18.0) 1 240,226 4.2 (0.1 – 23.2)

30–39 years

Males 5 341,527 14.6 (4.8 – 34.2) 3 197,554 15.2 (3.1 – 44.4)

Females 3 410,713 7.3 (1.5 – 21.3) 1 268,412 3.7 (0.1 – 20.8)

*Primary series surveillance for 18+ ended May 21, 2022, all other data through August 20, 2022.
VSD incidence rates of verified myocarditis/pericarditis in the 0–7 days after 

Moderna vaccination in people ages 12–39 years, dose 2 and 1st booster*

44 ***Primary series surveillance for 18+ ended May 21, 2022, all other data through August 20, 2022.

** Monitoring ongoing, no data provided if less than 2,500 doses given in a subgroup

Dose 2 primary series

Moderna

1

st booster dose

Moderna

Cases

Dose 2 

admin

Incidence rate/

million doses (95% CI) Cases

1

st boosters

admin

Incidence rate/

million doses (95% CI)

12–15 years

Males N/A N/A N/A N/A N/A N/A

Females N/A N/A N/A N/A N/A N/A

16–17 years

Males N/A N/A N/A N/A N/A N/A

Females N/A N/A N/A N/A N/A N/A

18–29 years

Males 19 195,809 97.0 (58.4 – 151.5) 7 109,337 64.0 (25.7 – 131.9)

Females 0 243,560 0.0 (0.0 – 12.3) 1 156,707 6.4 (0.2 – 35.6)

30–39 years

Males 8 216,583 36.9 (15.9 – 72.8) 1 149,468 6.7 (0.2 – 37.3)

Females 1 259,780 3.9 (0.1–21.4) 2 191,765 10.4 (1.3 – 37.7)
Myocarditis/pericarditis crude reporting rates per million doses 

administered following COVID-19 mRNA vaccines: 

Ontario, December 13, 2020 to August 14, 2022

https://www.publichealthontario.ca/-/media/Documents/nCoV/epi/covid-19-aefi-report.pdf?sc_lang=en

Age group 

(years)

Females: 

Dose 1

Females: 

Dose 2

Females: 

Dose 3

Males: 

Dose 1 

Males: 

Dose 2

Males: 

Dose 3

5-11* 3.2** 12.8 0 3.1** 8.2 0

12-17 36.8 33.1 0 75.4 164.4 60.0

18-24 29.5 46.8 0 56.1 202.4 35.7

25-29 15.2 31.4 8.1 58.5 77.7 14.5

Note: Includes all reports of myocarditis or pericarditis identified through case-level review (n=782), regardless of the reports meeting the Brighton Collaboration case definition for 

myocarditis or pericarditis. There are no myocarditis/pericarditis AEFIs reported in age group 0-4 years.

*The reporting rate for the 5-11 year age group only includes reports of myocarditis/pericarditis following Pfizer-BioNTech Comirnaty pediatric COVID-19 vaccine (10 mcg) authorized for this 

age group and doses administered of the Pfizer-BioNTech Comirnaty pediatric COVID-19 vaccine (10 mcg) product. There were four reports among those 11-year-olds (i.e., who turned 12 

years of age by the end of 2021) who received the Pfizer-BioNTech Comirnaty COVID-19 vaccine (30 mcg) indicated for 12+ years of age as per the provincial program. These reports are 

excluded from age group-specific reporting rate calculations but included in the total reporting rate calculation.

**Interpret with caution as this reporting rate is based on one report.
Key findings

▪ At least 90 days after myocarditis diagnosis, most patients who were reached reported 

no impact on their quality of life, and most did not report missing school or work

▪ 226 patients received a follow-up assessment: Most (80.1%) healthcare providers who 

completed surveys indicated the patient was fully recovered or probably fully recovered

– There was substantial heterogeneity in initial and follow-up treatment and testing

– There did not appear to be a single test that was indicative of recovery

CDC enhanced surveillance for myocarditis outcomes following 

mRNA COVID-19 vaccination in VAERS case reports:

Individuals ages 5–29 years

As previously presented to ACIP: 

https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-06-22-23/03-COVID-Shimabukuro-508.pdf 46
▪ Risk of myocarditis/pericarditis has been identified after COVID-19 vaccines

– Risk is rare and primarily observed in adolescent and young adult males

– Among VAERS data, reporting rates of myocarditis are lower after booster dose, compared to dose 2 

of primary series

– Among VSD data, incidence following dose 2 of primary series and booster dose are similar, but 

case counts are small

– Among surveillance data from Canada indicate that the risk of myocarditis and/or pericarditis 

following a first booster dose appear lower than the risk following second dose of a primary series

• Observed for both Pfizer-BioNTech and Moderna vaccine products and across all age groups1

▪ Most individuals with myocarditis/pericarditis have fully recovered at follow-up

▪ The risk of adverse cardiac outcomes were 1.8 – 5.6 times higher after SARS-CoV-2 infection 

than after mRNA COVID-19 vaccination among males ages 12 – 17 years2

▪ Interval of 8 weeks between vaccine doses may further lower myocarditis risk

Other considerations for COVID-19 vaccine boosters: 

Myocarditis and pericarditis

47

1. Public Health Agency of Canada. NACI: Recommendations on the use of bivalent Omicron-containing mRNA COVID-19 vaccines. Sept 1, 2022 2. DOI: http://dx.doi.org/10.15585/mmwr.mm7114e1
VaST reviews data from U.S. safety monitoring systems* as well as from other sources; 

through August 2022, VaST had held 64 teleconference meetings 

▪ COVID-19 mRNA vaccine booster doses:

v-safe: reactions and health impacts not higher after a booster dose than after primary 

series dose 2

VAERS: no additional concerns; myocarditis reporting rates lower after booster dose than 

after primary series dose 2 

VSD: few myocarditis/pericarditis cases after booster doses and risk estimates imprecise; 

risk after booster doses appears similar to risk after primary series dose 2

▪ Vaccination in pregnancy: no safety concerns from any of the systems that have data on 

primary series and first booster dose

▪ VaST will continue to review safety data, including data after bivalent vaccine booster

COVID-19 Vaccine Safety Technical (VaST) 

Work Group Assessment – Booster Doses

*Vaccine Adverse Event Reporting System (VAERS), v-safe, Vaccine Safety Datalink (VSD), Clinical Immunization Safety Assessment (CISA) project
COVID-19 Scenario Modeling Hub

▪ A multi-team effort aimed at creating and modeling planning scenarios for the mid- to long-term 

COVID-19 situation

▪ 5 – 10 submissions per scenario round at the national level

▪ Results are ensembled and summarized by the hub (as summarized by figure below)

▪ Round 14 and 15 were planning scenarios projecting COVID-19 burden through mid-2023 under 

different booster policies

49
Scenarios: Boosters and Variants

▪ Round 14

▪ VE of bivalent boosters assumed to be 80% against symptomatic disease with non-immune 

escape strains

▪ Targeted booster campaign ages ≥ 50 years vs. flu like uptake*in ages ≥ 18 years

▪ No variant vs. a fall “variant X” with 40% immune escape and 20% increased severity

▪ Data cutoff June 4, release July 19

▪ Round 15

▪ Rapid round aimed to update round 14 and consider booster timing

▪ Same VE and variant assumptions as round 14

▪ Scenario assumed booster recommendations with flu-like uptake*starting in September 2022 vs. 

November 2022

▪ Data cutoff July 30, release August 12 *Assumed 10% reduction of influenza

uptake in 2020–2021 season

~34% for adults ages 18–49 years

~50% for adults ages 50–64 years

~68% for adults ages ≥65 years

https://data.cdc.gov/Flu-Vaccinations/Influenza-VaccinationCoverage-for-All-Ages-6-Mont/vh55-3he6 50
https://covid19scenariomodelinghub.org/

Round 14: National 

ensemble projection 

intervals - Hospitalizations

Round 14 

Regardless of presence of a new 

variant, flu-like vaccine uptake in 

individuals ages ≥18 years

would lead to a 

>20% reduction in hospitalizations

and

>15% reduction in deaths

versus a recommendation for 

individuals ages ≥50 years only

51
https://covid19scenariomodelinghub.org/

Round 15: National 

ensemble projection 

intervals - Hospitalizations

Round 15 

Absent a new variant, boosters to 

individuals ages ≥18 years in September

could prevent 

137,000 more hospitalizations1

and 

9,700 more deaths2

compared to boosters in November

195% Confidence Interval: 21,000-251,000

295% Confidence Interval: 500-19,000 52
▪ Concern that giving additional doses of COVID-19 vaccine would lead to lower antibody 

levels (failure to restore antibody levels to what was seen after a previous dose) or T-cell 

exhaustion 

▪ Bivalent vaccine able to improve vaccine titers in individuals without prior SARS-CoV-2 

infection and provided a robust boost in antibody titers for individuals with prior 

infection

Other considerations: Immune tolerance

▪ High antibody titers for a 

bivalent vaccine and prior 

SARS-CoV-2 infection may 

lead to slower waning and 

prolonged protection against 

COVID-19 and severe disease

53
▪ Concern that initial exposure to one virus strain primes B-cell memory and limits the 

development of memory B cells and neutralizing antibodies against new strains

Other considerations: Imprinting

1. https://www.biorxiv.org/content/10.1101/2022.02.03.479037v1.full.pdf

2. https://assets.researchsquare.com/files/rs-1555201/v1_covered.pdf?c=1650045900

▪ Data suggest an improved diverse response 

obtained with bivalent vaccines

– Antibody titers to all SARS-COV-2 variants 

were higher with a bivalent vaccine, 

compared to monovalent ancestral 

vaccine

54
▪ Uses 2D and 3D maps to visualize how closely related the antibody responses are for 

different viruses

Other considerations: Antigenic cartography

▪ Antibody landscapes can evaluate diversity of immune response

– A ‘flat’ landscape is better, indicating that the responses to all viruses/variants were similar

– For the day 15 response (top landscapes), especially for those with prior infection (panel E): 

bivalent vaccine with prototype + Omicron provided a response that was diverse and similar across 

different variants 

https://www.medrxiv.org/content/10.1101/2022.07.12.22277336v1.full.pdf

Without prior infection With prior infection

55

Day 1 

Day 15 
▪ Clinical data from bivalent COVID-19 vaccines primarily obtained using BA.1 

▪ Compared to the ‘ancestral’ virus, all Omicron sub-lineages have 21 ‘shared’ mutations

– Highlighted by the black arrow

Other considerations: BA.1 and BA.4/BA.5

Evolution of the SARS‐CoV‐2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission - Shrestha - Reviews in Medical Virology - Wiley Online Library

▪ Many mutations are in the 

receptor binding domain (RBD), 

the primary binding site for 

antibodies

▪ These mutations contribute to 

decreased neutralization and 

increased transmissibility for 

Omicron sub-lineages

Shared by ALL 

Omicron 

sub-lineages

56
Other considerations: BA.1 and BA.4/BA.5

▪ BA.4/BA.5

– Two different Omicron sub-lineages, but Spike protein (focus of the vaccines) is identical 

– BA.4/BA.5 has additional mutations (in red), compared to previous Omicron lineages

57

Differences between BA.1 and BA.4/5:

NTD: 91, del 24-26, 95 ins214, del 143-145, 

RBD: 376, 405, 408, 446, 452, 486, 493, 496

S1/S2 interface: 547 S2: 856, 981

SARS-CoV-2 variants ~ ViralZone (expasy.org)
▪ Among residents of Qatar, vaccine effectiveness with 3 doses of Pfizer or Moderna 

COVID-19 vaccine showed higher effectiveness against symptomatic Omicron 

infection than previous SARS-CoV-2 infection alone

Other considerations: 

COVID-19 vaccination with and without prior SARS-CoV-2 infection

Altarawneh HN, Chemaitelly M, Ayoub HH, et.al. Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. N Engl J Med 2022; 387:21-34
Other considerations: Reinfection during Omicron

Individuals with recent prior SARS-CoV-2 infection are at reduced risk of Omicron infection and associated hospitalization (medrxiv.org)

▪ Among U.S. patients (EHR data), relative 

risk of SARS-CoV-2 infection for previously 

infected individuals was compared with a 

control cohort without previous infection, 

during each calendar month. 

▪ Reinfections were rare during the first year 

of the pandemic, and during Alpha and 

Delta surges in 2021, but the relative risk 

of infection in those with prior infection 

significantly increased during Omicron.
▪ Study assessed the benefits provided by homologous or 

heterologous vaccine boosters on vaccinee plasma 

neutralizing activity against Omicron sublineages

▪ Individuals who received a Novavax primary series and a 

Novavax booster had comparable neutralizing GMTs to 

those who received monovalent mRNA COVID-19 

vaccine as a primary series and booster

▪ Administration of a booster increased neutralizing 

antibody titers and breadth against Omicron sublineages

Other considerations: Non-mRNA boosters

DOI: 10.1126/science.abq020 
▪ Randomized trial of third dose booster vaccines given 10–12 weeks after an initial course of 

Pfizer-BioNTech COVID-19 primary series

▪ All booster doses resulted in increases anti-spike IgG concentrations. Third doses of mRNA vaccines 

resulted in geometric mean concentrations ~3x higher than those observed in Novavax recipients 

▪ All boosters showed acceptable side-effect profiles

Other considerations: Non-mRNA boosters

DOI: https://doi.org/10.1016/S0140-6736(21)02717-3

Booster dose Pfizer-BioNTech

n=23

Moderna

n=18

Novavax 

n=24

SARS-CoV-2 anti-spike IgG, ELU/mL

Day 0 5422 

(3781–7776)

3271 

(1970–5432)

3512 

(2454–5026)

Day 7 27551 

(21016–36118)

20930 

(11594–37786)

5080 

(3585–7199)

Day 28 26171 

(21245–32239)

30654 

(22916–41004)

8754 

(6262–12236)
Domain Equity Question:

Are the desirable and undesirable anticipated effects 

demonstrated across all populations equally?

62
▪ Are the desirable and undesirable 

anticipated effects demonstrated 

across all populations?

– Were persons of all races and ethnicities 

included in clinical trials or observations?

– Do the demographics of study populations 

reflect demographics of the US population?

– Are there specific population groups for which 

the burden of the public health problem or 

benefit of the intervention is of particular 

concern?

• If so, are these population groups represented 

in clinical trials or observations?

▪ Are the desirable and undesirable 

effects equally demonstrated across all 

populations?

– Were desirable and undesirable effects 

examined by population group?

– Are there any desirable or undesirable effects 

which appear more frequently in one or more 

population groups?

Are the desirable and undesirable anticipated effects 

demonstrated across all populations equally?

63
Characteristics n (%) mRNA-1273.214 (50 μg), 

N=437 

mRNA-1273 (50 μg), 

N=377 

US Census Data, 2021

Age subgroup

18-64 years 263 (60.2) 227 (60.2) 61

≥65 years 174 (39.8) 150 (39.8) 16.8%

Gender

Male 179 (41.0) 186 (49.3) 49.5%

Female 258 (59.0) 191 (50.7) 50.5%

Ethnicity

Hispanic or Latino 46 (10.5) 37 (9.8) 18.9%

Not Hispanic or Latino 390 (89.2) 340 (90.2) 81.1%

Race

White 381 (87.2) 322 (85.4) 75.8%

Black or African American 31 (7.1) 29 (7.7) 13.6%

Asian 14 (3.2) 16 (4.2) 6.1%

American Indian or Alaska Native 0 1 (0.3) 1.3%

Native Hawaiian or Other Pacific Islander 0 1 (0.3) 0.3%

Multiracial 7 (1.6) 2 (0.5) 2.9%

Moderna study 205 demographics 

https://www.medrxiv.org/content/10.1101/2022.06.24.22276703v1.full.pdf

U.S. Census Bureau QuickFacts: United States 64
Characteristics, % Substudy E US Census Data, 2021

Median age (years) 67 39

Sex

Male 49.5 49.5

Female 50.5 50.5

Ethnicity

Hispanic or Latino 14.9 18.9

Not Hispanic or Latino 85.1 81.1

Race

White 86.6 75.8

Black or African American 6.3 13.6

Asian 5.5 6.1

American Indian or Alaska Native ≤1.1 1.3

Native Hawaiian or Other Pacific Islander ≤1.1 0.3

Multiracial ≤1.1 2.9

Pfizer substudy E (age >55 years) expanded cohort 

demographics 

65
▪ Moderna bivalent booster data

– Omicron B.1 and original strain neutralizing antibodies after a 4th dose were 

comparable across racial groups

▪ Pfizer-BioNTech bivalent booster data

– Subgroups of participants >55 years of age in the safety population had generally 

similar adverse event profiles from study vaccination to 1 month post-dose, across 

various vaccine groups when evaluated by subgroups of sex, race, and ethnicity

– Overall, there were no clinically meaningful differences between subgroups for 

neutralizing GMTs for the Omicron variant and the original strain

▪ In both trials, subgroups of race and ethnicity included a limited number of 

participants, and their results should be interpreted with caution

Results by race and ethnicity 
Bivalent COVID-19 vaccines: 

Data to inform recommendations

▪ Experience from using COVID-19 vaccine mRNA platform for nearly 2 years and over 600 

million doses in the United States alone

– Extensive vaccine effectiveness studies as well as robust post-authorization safety data across multiple platforms

▪ Clinical (human) data from bivalent COVID-19 vaccines in >1700 persons

– Includes bivalent vaccines with Beta and Omicron variants, both from manufacturers and NIH studies

– Over 1400 individuals received bivalent vaccine with Omicron component specifically

– While there are subtle differences in mutations between BA.1 and BA.4/BA.5 spike protein sequences, 

do not anticipate differences in safety or reactogenicity of vaccines based on these limited mutations

– Overall composition of the vaccine as well as total antigenic load are the same as current booster doses

▪ Antigenic cartography and antibody studies 

▪ Modeling data

67
Bivalent COVID-19 vaccines: 

What we know

▪ COVID-19 vaccines have a high degree of safety

– Rare events of myocarditis seen after mRNA COVID-19 vaccines in post-authorization studies; 

cases of myocarditis attributed to the vaccine were detected in Novavax COVID-19 vaccines clinical trials 

▪ COVID-19 vaccines provide high levels of protection against severe disease

– Initially, COVID-19 vaccines also provided high levels of protection against infection and transmission 

– As the virus evolved, noted rapid waning of protection against asymptomatic or mild disease

▪ COVID-19 booster doses further increase protection against severe disease

▪ Bivalent COVID-19 vaccines expand immune response after vaccination

– Vaccines that contain Omicron will improve antibody response to Omicron

– Bivalent vaccines appear to provide more diverse response overall, likely improving response to future 

variants 

68
Bivalent COVID-19 vaccines: 

What we do not know

▪ Rate of myocarditis after bivalent COVID-19 vaccines

– Unlikely that the inclusion of Omicron would increase myocarditis rates

– Age and sex of the individual are likely contributing factors to development of myocarditis after vaccine; 

interval since previous dose and total dose may be related

▪ Incremental increase in vaccine effectiveness

– Antibody titers to currently circulating variants were higher after a bivalent booster than with current 

monovalent booster

– Most of the data to inform recommendations from BA.1 bivalent vaccine; incremental benefits for the 

BA.4/BA.5 vaccine are unknown 

▪ Duration of protection 

– Antibody titers after bivalent vaccine and prior SARS-CoV-2 infection were robust

– This may prolong duration of protection and decrease the need for frequent boosters

– As with all vaccines, duration of protection may vary by age and immune status 69
Summary-balance of benefits and harms for bivalent booster doses 

▪ Bivalent booster dose of both Moderna & Pfizer-BioNTech COVID-19 vaccines increases 

immune response in those who have completed a primary series and a previous booster

▪ Similar reactogenicity profile to primary series and ancestral booster dose

▪ Myocarditis risk following a bivalent booster dose is unknown, but anticipate similar risk to 

what is seen after monovalent booster doses

▪ Modeling projects more hospitalizations and deaths averted when booster doses are 

recommended for persons ≥18 years compared to only persons ≥50 years, and when the 

booster campaign begins in September compared to November 2022

▪ Benefits and harms for the U.S. population are best assessed when clinical trial and study 

populations are optimally representative of the U.S. population 

70
Benefits and Harms

How substantial are the desirable anticipated effects?

• How substantial are the anticipated effect for each main outcome for which 

there is a desirable effect?

o Minimal o Small o Moderate o Large o Varies o Don’t know
Benefits and Harms

How substantial are the undesirable anticipated effects?

• How substantial are the anticipated effect for each main outcome for which 

there is an undesirable effect?

o Minimal o Small o Moderate o Large o Varies o Don’t know
Benefits and Harms

Do the desirable effects outweigh the undesirable effects?

• What is the balance between the desirable effects relative to the 

undesirable effects?

o Favors intervention (updated (bivalent) COVID-19 vaccine booster doses)

o Favors comparison (no vaccine)

o Favors both

o Favors neither

o Unclear
EtR Domain: Values
72% of respondents “definitely” or “probably” will get an updated booster 

that protects against Omicron variants

‘Probably’ or 

‘Definitely’ will get 

an updated booster

Unsure

‘Probably’ or 

‘Definitely’ will not get 

an updated booster

CDC and University of Iowa/RAND survey, August 2022, unpublished n=171
33.3%

31.3%

27.1%

25.0%

22.9%

16.7%

14.6%

14.6%

12.5%

4.2%

2.1%

2.1%

2.1%

0.0%

0.0%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Have enough protection from previous doses

Updated booster is not effective

COVID not a threat to personal health

Just don't want any more COVID vaccine shots

Have enough protection from COVID-19 infection

Worried about side effect from updated booster

Updated booster is not safe

Had about side effects from previous doses

Other

Can't miss work if sick after booster

No time to get booster

Fear of needles

Not due for a booster

Don't know

Refuse to answer

% of respondents who selected response option

Belief that previous doses provided enough protection and doubts about an 

updated vaccine’s efficacy were the most selected reasons for being unsure or not 

intending to get an updated booster (n=48).

CDC and University of Iowa/RAND survey, August 2022, unpublished 
46.2%

38.0%

31.6%

29.8%

29.2%

29.2%

27.5%

25.7%

22.8%

19.9%

18.7%

14.6%

11.7%

10.5%

9.9%

8.8%

8.2%

4.7%

4.1%

1.8%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Prevent me from spreading to others

Cases became more severe

Increase of cases in my area

New variants

More information showing vaccine works

Allow me to travel

HCP recommendation

More information showing vaccine is safe

Workplace mandate

It would allow me to do social activities

Someone I knew became ill or died

No longer need to wear mask

Friend or family recommendation

Business mandate

Allow me to go to work

None of these

Community getting vaccinated

Faith leader recommendation

School mandate

Other

% of respondents who selected response option

Preventing spread to others and change in case severity were the most 

selected facilitators to getting an updated booster.

CDC and University of Iowa/RAND survey, August 2022, unpublished n=171
63% of respondents were “extremely” or “somewhat” willing get an annual flu 

shot and updated COVID booster at the same visit this Fall

‘Somewhat’ or 

‘Extremely’ willing to 

get both vaccines in 

the same visit this Fall

Unsure

‘A bit’ or ‘Not at all’ 

willing to get both 

vaccines in the same 

visit this Fall

n=171 CDC and University of Iowa/RAND survey, August 2022, unpublished 
Domain Equity Question:

Is there important variability in how patients or populations 

value the outcome?

79
▪ Booster uptake has remained relatively steady, with those groups with higher initial 

vaccine uptake also more likely to have received their booster dose

▪ Overall, around half of adults report being fully vaccinated and have received their 

booster dose for COVID-19 (49%), with the largest shares among adults ages 65 and 

over (76%), college graduates (67%) and those with a household income of $90K+ 

(62%)

▪ Notably, despite a high vaccine uptake rate (83%), about a third of adults of 

Hispanic/Latino ethnicity (33%) say they’re fully vaccinated for COVID-19 but haven’t 

received their booster dose yet

Older adults, college graduates and those with higher incomes 

remain most likely to be vaccinated and boosted 

The survey was conducted July 7 – 17, 2022, online and by telephone among a nationally representative sample of 1,847 U.S. adults.

KFF COVID-19 Vaccine Monitor: July 2022. https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-july-2022/ Accessed August 9, 2022 80
▪ Percent of vaccinated adults without a booster who say the following is a reason they 

have not received a COVID-19 booster dose:

Majority of vaccinated adults feel protection from initial vaccine 

or prior infection is primary reason for not receiving a booster 

The survey was conducted July 7 – 17, 2022, online and by telephone among a nationally representative sample of 1,847 U.S. adults.

KFF COVID-19 Vaccine Monitor: July 2022. https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-july-2022/ Accessed August 9, 2022 81
▪ 72% of survey respondents reported they were likely to receive an updated COVID-19 booster 

▪ Preventing spread to others (46.2%) and change in case severity (38%) were the top facilitators to 

getting an updated booster 

– Whereas belief that previous doses provided enough protection (33.3%) and doubts about an updated 

vaccine’s efficacy (31.3%) were the top deterrents for being unsure or not intending to get an updated booster

▪ Nearly 2/3 of adults were willing to receive an updated COVID-19 vaccine and an influenza shot at the 

same time

▪ Receipt of booster to date demonstrates persistent vaccine inequity

– Adults of older age, with college degrees, and with higher incomes remain most likely to be vaccinated and 

boosted

– ~33% of adults of Hispanic/Latino ethnicity have not received a booster despite completion of primary series

Summary

Values

82
Values

Criteria 1:

Does the target population feel that the desirable effects are large relative to 

undesirable effects?

• How does the target population view the balance of desirable versus undesirable 

effects? 

• Would patients/caregivers feel that the benefits outweigh the harms and burden?

• Does the population appreciate and value the Bivalent COVID-19 vaccine booster?

o Minimal o Small o Moderate o Large o Varies o Don’t know
Values

oImportant uncertainty or variability

oProbably important uncertainty or variability

oProbably not important uncertainty or variability

oNo important uncertainty or variability

oNo known undesirable outcomes

Criteria 2:

Is there important uncertainty about, or variability in, how much people value 

the main outcomes?

• How much do individuals value each outcome in relation to the other outcomes?

• Is there evidence to support those value judgements?

• Is there evidence that the variability is large enough to lead to different decisions?
EtR Domain: Acceptability
86

Infrastructure Exists to Reach Key Populations:

U.S. COVID-19 Vaccine Program Milestones (August 2022)

Source: Data pulled from CDC COVID Data Tracker as of 08/17/22 1200

Over 800 million 

doses delivered

in 88 weeks

Over 606 million doses 

administered

in 87 weeks

About 90% of 18+ 

population have 

received at least 1 

dose

About 92% of 65+ 

population are fully 

vaccinated with 71% 

boosted

Over 223 million 

people fully 

vaccinated
Jurisdictional Providers 

(~48K)

Pharmacy Providers 

(~38K)

Federal Providers 

(~1,500)

FQHCs

U.S. Network of Active COVID-19 Vaccine Providers 
Domain Equity Question:

Is the intervention equally acceptable across all populations?

88
Percent of population with a completed COVID-19 primary 

series in the United States, by race and ethnicity 

CDC COVID Data Tracker. Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States. https://covid.cdc.gov/covid-datatracker/#vaccination-demographics-trends Accessed August 31, 2022

December 14, 2020 – August 24, 2022

89
Booster vaccination coverage in the United States,

by race and ethnicity 

CDC COVID Data Tracker. Trends in Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States. https://covid.cdc.gov/covid-datatracker/#vaccination-demographics-trends Accessed August 31, 2022

August 12, 2021 – August 24, 2022

90
Average percentages of fully vaccinated population with a first 

booster dose in the United States, by county urbanicity 

CDC COVID Data Tracker. COVID-19 Vaccination Equity. https://covid.cdc.gov/covid-data-tracker/#vaccination-equity Accessed August 31, 2022 91
Reported receipt of COVID-19 booster doseƗ among fully vaccinatedƗƗ adults 

ages 18 years and older by disability status** and race and ethnicity, 

Household Pulse Survey, March 30, 2022 – May 9, 2022,˄˄ United States

CDC COVID Data Tracker. COVID-19 Vaccination among People with Disabilities. https://covid.cdc.gov/covid-data-tracker/#vaccinations-disability-status Accessed August 25, 

2022 92
▪ A poll from the University of Michigan found that 77% of older adults say their 

provider’s recommendation about COVID-19 vaccination is very or somewhat 

important to their decision to get vaccinated

▪ The percentage saying a provider’s recommendation was very important was highest 

for those who were Black (79%), over age 65, retired or have incomes under $30,000 

(56%, respectively) compared with those of other racial and ethnic backgrounds, 

work statuses or income levels

▪ Physicians, nurses and nurse practitioners, pharmacists and physician’s assistants 

should start communicating to their patients now about the importance of getting a 

dose of one of the updated (bivalent) COVID-19 boosters when they become 

available

Importance of providers’ recommendation in COVID-19 vaccine 

acceptability 

Institute for Healthcare Policy and Innovation. University of Michigan. August 9, 2022. Most older adults are ready to roll up sleeves this fall for updated COVID-19 boosters, UM poll shows. https://ihpi.umich.edu/news/most-older-adults-ready-roll-sleeves-fall-updated-covid-19-boosters-u-m-poll-shows Accessed August 24, 2022 93
▪ Over 800 million doses of COVID-19 vaccines have been delivered since the 

beginning of the program, with a wide network of vaccine providers

▪ Significant disparities in completion of primary series vaccination and receipt of 

booster doses persist by race, ethnicity, urbanicity, and differences in abilities 

including vision, hearing, mobility and cognition

▪ Detection of disparities does not explain disparities:

– Differences in acceptability may contribute to disparities

– Differences in access may contribute to disparities

– Identifying and understanding these and other drivers of inequity is a critical step toward equity

▪ Healthcare provider recommendation continues to appear to increase acceptability 

of COVID-19 vaccination, and particularly among adults who are Black, over the age 

of 65, retired, and/or of lower income

Summary 

Acceptability 

94
Acceptability

Is the updated (bivalent) COVID-19 vaccine booster acceptable to 

key stakeholders?

• Are there key stakeholders that would not accept the distribution of benefits 

and harms? 

• Are there key stakeholders that would not accept the undesirable effects in 

the short term for the desirable effects (benefits) in the future?

oNo oProbably no oProbably yes oYes oVaries oDon’t know
EtR Domain: Feasibility
Completed primary series and 1

st boosters by age group for 

persons ages 5-49 years, United States, December 2020 –

August 2022

0

1

2

3

4

5

6

7

Completed Primary Series and 1st 

Boosters (M)

Primary Series: Ages 5-11 1st Booster: Ages 5-11

Primary Series: Ages 12-17 1st Booster: Ages 12-17

Primary Series: Ages 18-49 1st Booster: Ages 18-49

Source: CDC IZDL; Accessed 8/22/22; First boosters

does not include Texas for all ages or 

Idaho for ages <18

For most individuals ages 5–49 years, 

it has been 6 months or more since 

their last COVID-19 vaccine 
Completed primary series, 1

st boosters, and 2nd boosters

by age group for persons ages ≥50 years, United States, 

December 2020 – August 2022

Source: CDC IZDL; Source: CDC IZDL; Accessed 8/22/22; First and second booster not include Texas for all ages or Idaho for ages <18 

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Completed Primary Series, 1st and 2nd, 

Boosters (M)

Primary Series: Ages 50-64 1st Booster: Ages 50-64 2nd Booster: Ages 50-64

Primary Series: Ages 65+ 1st Booster: Ages 65+ 2nd Booster: Ages 65+
Age Group Eligible*

persons

(millions)

Ineligible+ persons

(millions)

12-17 years 14 0.3 

18-49 years 96 0.7 

50-64 years 51 1.6 

≥65 years 48 2.0

Total 209 4.6

Persons eligible* (in millions) for a bivalent booster by age group 

– United States, December 2020 – August 2022

Source: CDC IZDL; Source: CDC IZDL; Accessed 8/22/22; First and second booster not include Texas for all ages or Idaho for ages <18 

*

Individuals are considered eligible if they had completed at least a primary series but had not received a vaccine dose in the prior 2 months

+

Individuals are considered ineligible if they received a vaccine dose within the previous 2 months per EUA

Based on dates of 9/2/2022 
▪ The U.S. Government has purchased approximately 171 million bivalent mRNA 

COVID-19 vaccine booster doses for the fall and beyond

▪ There will be a sufficient but finite supply of updated (bivalent) COVID-19 vaccines, 

which should be directed to providers with expected demand among eligible patients 

▪ Considerations for selecting sites to receive the initial doses include:

Jurisdictional planning and considerations 

CDC Fall Vaccination Operational Planning Guide – Information for the Fall Vaccine Campaign, Including Upcoming Bivalent COVID-19 Vaccine Booster Doses. 

https://www.cdc.gov/vaccines/covid-19/downloads/CDC-Fall-Vaccination-Operational-Planning-Guide.pdf Accessed August 19, 2022 

– Location and access to a range of populations and 

ensuring that distribution to these groups is 

equitable to the extent possible

– Ability to reach eligible persons at highest risk for 

severe COVID-19 (e.g., older adults, long-term care 

facility residents, people with certain medical 

conditions)

– Ability to handle 100-dose & 300-dose product 

configurations

– Ability to administer both Pfizer-BioNTech and Moderna 

bivalent vaccines to meet anticipated community demand

– Ability to efficiently vaccinate within 12 hours once a vial is 

opened

– Ability to manage inventory to ensure availability of 

primary series doses, in addition to bivalent booster doses, 

in their local area when feasible

– Overall readiness (e.g., staffing, scheduling capabilities)

100
▪ The bivalent vaccines will have the same storage and handling parameters as the 

monovalent vaccine products

▪ Both manufacturers’ bivalent vaccines have grey label border, but different injection 

volume

– Pfizer-BioNTech vaccine labels for both the monovalent and bivalent vials will have an 

identical grey cap/grey label border presentation

– Moderna bivalent vaccine will have dark blue cap/grey label border (similar to monovalent 

product for ages 6–11 years)

• Will be different from the red cap/light blue label border for the adult monovalent vaccine

Implementation for bivalent COVID-19 vaccine booster doses 

CDC Fall Vaccination Operational Planning Guide – Information for the Fall Vaccine Campaign, Including Upcoming Bivalent COVID-19 Vaccine Booster Doses. 

https://www.cdc.gov/vaccines/covid-19/downloads/CDC-Fall-Vaccination-Operational-Planning-Guide.pdf Accessed August 19, 2022 101
Domain Equity Question:

Is the intervention equally feasible to implement across all 

populations?

102
Percentages of population eligible for a first booster dose* with 

and without a booster, by race and ethnicity 

CDC COVID Data Tracker. Demographic Characteristics of People Receiving COVID-19 Vaccinations in the United States. https://covid.cdc.gov/covid-data-tracker/#vaccinationdemographic Accessed August 27, 2022

Data from 193.55M people ages 12 years and older who are eligible for a booster dose*. Race and ethnicity 

was available for 148.95M (77%) people ages 12 years and older who are eligible for a booster dose.

103
▪ Over 200 million people would be eligible for the bivalent COVID-19 vaccine

▪ While nearly 22 million adults >50 years have received a second booster dose,

most individuals ages 5 years and older are at least 6 months out from their last 

COVID-19 vaccine dose

▪ CDC has provided an Operational Planning Guide for jurisdictions preparing for a fall 

vaccination campaign

▪ There will be a sufficient but finite supply of bivalent COVID-19 vaccines

▪ Some aspects of the bivalent COVID-19 vaccines will be easy to implement (no changes 

to storage/handling), but vials and labeling may need additional education

▪ Significant racial and ethnic disparities persist in receipt of a booster, suggesting that 

the intervention may not be equally feasible to implement across all populations

Summary 

Feasibility 

104
Feasibility

Is the updated (bivalent) COVID-19 vaccine booster feasible to

implement among populations currently recommended for a 

booster?

• Is the updated (bivalent) COVID-19 vaccine booster program sustainable?

• Are there barriers that are likely to limit the feasibility of implementing the 

updated (bivalent) COVID-19 vaccine booster or require considerations when 

implementing it? 

• Is access to the updated (bivalent) COVID-19 vaccine booster an important 

concern?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
EtR Domain: Resource Use
Projected COVID-19-attributable deaths, hospitalizations, infections and 

direct medical costs averted by the U.S. booster vaccination program under 

two potential scenarios between August 1, 2022, and March 31, 2023

Abhishek Pandey et al., “How Many Lives Could a Fall COVID-19 Booster Campaign Save in the United States?,” To the Point (blog), Commonwealth Fund, July 26, 

2022. https://doi.org/10.26099/rc8x-dx51 107
Projected direct medical cost savings and vaccination program 

costs for each booster vaccination scenario 

Abhishek Pandey et al., “How Many Lives Could a Fall COVID-19 Booster Campaign Save in the United States?,” To the Point (blog), Commonwealth Fund, July 26, 

2022. https://doi.org/10.26099/rc8x-dx51 108

In $ billions

Scenario 1:

Flu-like vaccination coverage for booster eligible population 

In $ billions

Scenario 2:

80% of population eligible for booster doses are vaccinated 
Domain Equity Question:

Is the intervention a reasonable and efficient allocation of 

resources across all populations?

109
▪ Cost-effectiveness data not yet available for most demographic subgroups, but some 

information is available for older adults

▪ Study evaluated cost-effectiveness of the first booster dose of the Pfizer-BioNTech 

COVID-19 vaccine (monovalent), administered 6 months after the second dose, 

among adults ≥65 years from a healthcare system perspective

▪ Compared with 2 doses of COVID-19 vaccine without a booster, the booster strategy 

in 100,000 older adults would result in a net monetary benefit of $3.4 million and a 

gain 3.7 quality-adjusted life-years in 180 days

▪ While cost-effectiveness of the boosters is highly sensitive to the population 

incidence of COVID-19 and vaccine effectiveness, offering the COVID-19 boosters to 

adults age ≥65 years in the United States is likely to be cost-effective

Cost-effectiveness of booster vaccination in persons ≥65 years

https://doi.org/10.1016/j.ijid.2022.03.029 110
▪ A fall vaccination campaign that expands eligibility for boosters and moves more 

aggressively to reach people could avert a surge of hospitalizations and deaths

▪ Additionally, an early fall vaccination campaign could avert between $63 billion and 

$109 billion in medical costs, depending on level of booster coverage achieved, with 

the majority of savings resulting from averted hospitalizations, particularly in the ICU

Summary 

Resource Use

Abhishek Pandey et al., “How Many Lives Could a Fall COVID-19 Booster Campaign Save in the United States?,” To the Point (blog), Commonwealth Fund, July 26, 

2022. https://doi.org/10.26099/rc8x-dx51 111
Resource Use

Is the updated (bivalent) COVID-19 vaccine booster a reasonable 

and efficient allocation of resources?

• What is the cost-effectiveness of the updated (bivalent) COVID-19 vaccine 

booster?

• How does the cost-effectiveness of the updated (bivalent) COVID-19 vaccine 

booster change in response to changes in context, assumptions, etc.?

o No o Probably no o Probably yes o Yes o Varies o Don’t know
Summary 
Summary

114

Moderna COVID-19 vaccine

50μg of spike protein from

‘ancestral’ (‘original’) SARS-CoV-2

Current (Monovalent) COVID-19 vaccines

Pfizer-BioNTech COVID-19 vaccine

30μg of spike protein from

‘ancestral’ (‘original’) SARS-CoV-2

Moderna COVID-19 vaccine

25μg of spike protein from

‘ancestral’ (‘original’) SARS-CoV-2

Updated (Bivalent) COVID-19 vaccines

Pfizer-BioNTech COVID-19 vaccine

15μg of spike protein from

‘ancestral’ (‘original’) SARS-CoV-2

25μg of spike protein from

Omicron (BA.4/BA.5) SARS-CoV-2

15μg of spike protein from

Omicron (BA.4/BA.5) SARS-CoV-2

50μg

30μg

50μg

30μg

Bivalent vaccines have the 

same total antigen amount 

as monovalent vaccines 
▪ Current (monovalent) COVID-19 vaccines have dramatically reduced COVID-19 

hospitalizations and deaths

▪ As the SARS-Cov-2 virus evolved, declines in neutralizing antibodies and vaccine 

effectiveness as well as more rapid waning from the vaccines noted

▪ Inclusion of a second SARS-CoV-2 variant in the vaccine broadens the antibody response

▪ Omicron-specific bivalent COVID-19 vaccines were studied in over 1400 individuals

▪ Omicron-specific bivalent COVID-19 vaccine resulted in:

– Higher antibody titers for Omicron variants

– Higher titers for other SARS-CoV-2 variants

– Titers that were as high or higher for ancestral SARS-CoV-2

▪ Broad uptake of COVID-19 vaccine booster doses early this fall could prevent >100,000 

hospitalizations, compared to later or more limited roll-out; in addition, billions of 

dollars of direct medical costs could be saved

Summary 

115
Work Group Interpretation 

116

▪ Work Group had broad policy discussions around use of updated (bivalent) COVID-19 

vaccines for all people of age groups currently recommended for booster doses

▪ Based on current FDA authorizations, current recommendations would be:

– Pfizer-BioNTech COVID-19 vaccine, bivalent for individuals ages 12 and older

– Moderna bivalent COVID-19 vaccine, bivalent for individuals ages 18 and older

▪ Additional authorizations for other ages and vaccines may follow
Work Group Interpretation 

117

▪ Current population recommended for these boosters is very heterogenous

– Many in the United States had Omicron infection over the past 9 months

– Individuals recommended for the bivalent COVID-19 booster doses may have previously 

received:

• Primary series only

• One booster dose

• Two booster doses (for those 50 years and over) 

▪ Balance of benefits and risks for individuals may vary by age, previous receipt of 

booster, or recent SARS-CoV-2 infection

▪ Uncertainties around the incremental benefits for some individuals, including those 

recent infection or recent vaccine receipt
Work Group Interpretation 

118

▪ COVID-19 vaccines are recommended, even for those with prior infection

– Rate of reinfections increased during the Omicron period 

▪ Bivalent COVID-19 vaccines in the setting of prior SARS-CoV-2 infection (“hybrid 

immunity”) resulted in highest antibody titers

– These high and diverse titers may result in longer duration of protection and 

decreased need for frequent COVID-19 vaccine booster doses

▪ Studies have shown that increased time between infection and vaccination may 

result in an improved immune response to vaccination

– Those with recent SARS-CoV-2 infection may consider delaying a vaccine dose by 

3 months from symptom onset or positive test
Work Group Interpretation 

119

▪ Time since most recent COVID-19 vaccine dose may be more important than 

cumulative number of doses

▪ There will be a time of transition as recommendations may move from counting dose 

number to optimal timing of vaccination campaigns

▪ Vaccine recommendations that are simple and easy to communicate are important 

▪ If SARS-CoV-2 becomes a seasonal virus, an annual vaccine program could be an 

effective strategy for the future
EtR Domain Question(s) Domain Equity Question(s)

Public Health 

Problem

• Is the problem of public health importance? • Does the problem impact all populations equally?

Benefits and 

Harms

• How substantial are the desirable anticipated effects?

• How substantial are the undesirable anticipated 

effects?

• Do the desirable effects outweigh the undesirable 

effects?

• Are the desirable and undesirable anticipated effects 

demonstrated across all populations equally?

Values • Does the population feel the desirable effects are 

large relative to the undesirable effects?

• Is there important variability in how patients or 

populations value the outcome?

Acceptability • Is the intervention acceptable to key stakeholders?

• Is the intervention equally acceptable across all 

populations?

Feasibility • Is the intervention feasible to implement? • Is the intervention equally feasible to implement 

across all populations?

Resource Use • Is the intervention a reasonable and efficient 

allocation of resources?

• Is the intervention a reasonable and efficient 

allocation of resources across all populations?

120
▪ There are many social, geographic, economic and environmental factors that create challenges to 

vaccination access and acceptance, and that often affects racial and ethnic minority groups1

▪ A few key activities for readiness and response for equitable access to updated (bivalent) COVID-19 

vaccine booster doses entail:

▪ Supply and ordering readiness

– Determine which provider locations will receive initial vaccine supply, balancing equitable access with 

vaccination capacity and consideration of initial demand

▪ Provider readiness

– Ensure providers are enrolled to reach key populations; identify providers who are not yet COVID-19 

vaccination providers and facilitate their enrollment, especially providers who can fill a geographic gap in 

access and providers who care for people who are at increased risk for developing severe outcomes

– Ensure providers are aware of resources to help support coadministration of COVID-19 vaccines and other 

vaccines, including influenza vaccines, during a visit

– Encourage providers who are not able to offer COVID-19 vaccination to refer their patients to nearby 

vaccination providers2

Implementation and Considerations for Equity

1. CDC. COVID-19 Vaccine Equity for Racial and Ethnic Minority Groups. https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/vaccine-equity.html

Accessed August 30, 2022

2. CDC Fall Vaccination Operational Planning Guide – Information for the Fall Vaccine Campaign, Including Upcoming Bivalent COVID-19 Vaccine Booster Doses. 

https://www.cdc.gov/vaccines/covid-19/downloads/CDC-Fall-Vaccination-Operational-Planning-Guide.pdf Accessed August 30, 2022 
▪ Communication also plays an integral role in ensuring equitable access to updated (bivalent) COVID19 vaccine booster doses 

▪ Additional readiness and response activities entail the following:

– Create a communication plan that outlines strategies, audiences, and products that will be used to promote 

COVID-19 vaccination of unvaccinated key populations and populations recommended for bivalent booster 

vaccination

– Understand existing data, attitudes, and perceptions regarding COVID-19 vaccination (including coadministration with influenza vaccine) in terms of demand, provider types, and locations where vaccination 

would be preferred

• Share these data with local jurisdictions and partners to help shape messages

– Develop communication products for providers, pharmacies, and the public that align with federal messaging 

and ensure communication materials are culturally and linguistically appropriate

– Leverage partnerships to help mobilize providers and promote COVID-19 bivalent booster vaccination 

messaging

– Engage and educate partners and trusted messengers (e.g., healthcare professionals, community leaders, faith 

leaders and faith-based organizations) as soon as possible

Implementation and Considerations for Equity, cont’d 

CDC Fall Vaccination Operational Planning Guide – Information for the Fall Vaccine Campaign, Including Upcoming Bivalent COVID-19 Vaccine Booster Doses. 

https://www.cdc.gov/vaccines/covid-19/downloads/CDC-Fall-Vaccination-Operational-Planning-Guide.pdf Accessed August 30, 2022 
123

EtR DomainQuestionWork Group Judgments

Public Health 

Problem

Is COVID-19 of public health importance?Yes

Benefits and 

Harms

How substantial are the desirable anticipated effects? Moderate

How substantial are the undesirable anticipated effects? Small

Do the desirable effects outweigh the undesirable effects? Favors intervention

Values

Does the target population feel the desirable effects are large 

relative to the undesirable effects?

Moderate 

Is there important variability in how patients value the outcomes? Probably important uncertainty 

or variability 

Acceptability

Is the Bivalent COVID-19 vaccine booster acceptable to key 

stakeholders?

Probably yes

Feasibility

Is the Bivalent COVID-19 vaccine booster feasible to implement?Probably yes

Resource Use

Is the Bivalent COVID-19 vaccine booster a reasonable and 

efficient allocation of resources?

Probably yes
124

Evidence to Recommendations Framework

Summary: Work Group Interpretations

Balance of 

consequences

Undesirable 

consequences 

clearly 

outweigh 

desirable 

consequences 

in most 

settings

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences 

in most 

settings

The balance 

between 

desirable and 

undesirable 

consequences 

is closely 

balanced or 

uncertain

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences 

in most 

settings

Desirable 

consequences 

clearly 

outweigh 

undesirable 

consequences 

in most 

settings

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences
125

Evidence to Recommendations Framework

Summary: Work Group Interpretations

Type of 

recommendation

We do not recommend 

the intervention

We recommend the 

intervention for individuals 

based on shared clinical 

decision-making

We recommend the 

intervention 
Question to ACIP 

▪ Should updated (bivalent) vaccines be recommended for persons already 

recommended to receive a COVID-19 vaccine booster dose? 

Products and ages currently authorized by FDA include:

Moderna COVID-19 vaccine for ages 18 years and older

Pfizer-BioNTech COVID-19 vaccine for ages 12 years and older
▪ Monica Godfrey

▪ Evelyn Twentyman 

▪ Megan Wallace

▪ Hannah Rosenblum

▪ Lauren Roper

▪ Danielle Moulia

▪ Joy Hsu

▪ Katherine Fleming-Dutra

▪ Sarah Meyer

▪ Susan Goldstein

▪ Mary Chamberland

▪ Elisha Hall

▪ Valerie Morelli

▪ JoEllen Wolicki

▪ Meg Freedman

▪ Heather Scobie

▪ Ruth Link-Gelles

▪ Sierra Scarbrough

▪ Jefferson Jones

▪ Stephen Hadler

▪ Epi Task Force

▪ Data Analytics and Visualization Task Force

▪ Respiratory Viruses Branch

▪ National Center for Immunization and Respiratory 

Diseases

Acknowledgments
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

Thank you
129

ACIP Vote #1

A single dose of bivalent Pfizer-BioNTech COVID-19 vaccine

is recommended for individuals ages 12 years and older 

at least 2 months after receipt of a primary series or prior monovalent 

booster dose, under the EUA issued by FDA

ACIP repeals its previous recommendations for administration of 

monovalent Pfizer-BioNTech COVID-19 vaccine boosters

for persons ages 12 years and older

Bivalent booster recommendations are without regard to the number of previous monovalent booster doses received
130

ACIP Vote #2

A single dose of bivalent Moderna COVID-19 vaccine 

is recommended for individuals ages 18 years and older 

at least 2 months after receipt of a primary series or prior monovalent 

booster dose, under the EUA issued by FDA

ACIP repeals its previous recommendations for administration of 

monovalent Moderna COVID-19 vaccine boosters

for persons ages 18 years and older

Bivalent booster recommendations are without regard to the number of previous monovalent booster doses received
▪ We are asking for ACIP feedback on the overall updated recommendation strategy

– More in line with traditional ACIP recommendations and a broad summary of the program

ACIP discussion 

131

Primary 

Dose

Primary 

Dose

Bivalent 

Booster

People ages 5 years and older*

Proposed updated recommendations

*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC

Regardless of previous booster doses given

▪ CDC will review any additional data to consider expansion of age groups recommended for 

bivalent COVID-19 vaccines

▪ Future recommendations would necessarily follow updates to the EUAs issued by FDA