Evidence to Recommendations Framework and Policy Options: 

Use of 20-valent Pneumococcal Conjugate Vaccine in U.S. Children

Miwako Kobayashi, MD, MPH

Pneumococcal Vaccines Work Group

Advisory Committee on Immunization Practices

June 22, 2023

National Center for Immunization & Respiratory Diseases
PICO 

Question

Should PCV20 be recommended as an option for pneumococcal vaccination 

for U.S. children?

Population All U.S. children aged <2 years U.S. children aged 2–18 years with 

underlying medical conditions

Intervention

PCV20 according to currently 

recommended dosing and 

schedules

PCV20 (without PPSV23)

Comparison PCV13 or PCV15 according to currently recommended dosing and schedules

Outcomes VT-IPD, VT- pneumonia, VT- AOM, VT- pneumococcal deaths, serious adverse 

events following vaccination

VT: vaccine-type, IPD: invasive pneumococcal disease, AOM: acute otitis media 2
PICO 

Question

Should PCV20 be recommended as an option for pneumococcal vaccination 

for U.S. children?

Population All U.S. children aged <2 years U.S. children aged 2–18 years with 

underlying medical conditions

Intervention

PCV20 according to currently 

recommended dosing and 

schedules

PCV20 (without PPSV23)

Comparison PCV13 or PCV15 according to currently recommended dosing and schedules

Outcomes VT-IPD, VT- pneumonia, VT- AOM, VT- pneumococcal deaths, serious adverse 

events following vaccination

VT: vaccine-type, IPD: invasive pneumococcal disease, AOM: acute otitis media 3
PICO 

Question

Should PCV20 be recommended as an option for pneumococcal vaccination 

for U.S. children?

Population All U.S. children aged <2 years U.S. children aged 2–18 years with 

underlying medical conditions

Intervention

PCV20 according to currently 

recommended dosing and 

schedules

PCV20 (without PPSV23)

Comparison PCV13 or PCV15 according to currently recommended dosing and schedules

Outcomes VT-IPD, VT- pneumonia, VT- AOM, VT- pneumococcal deaths, serious adverse 

events following vaccination

VT: vaccine-type, IPD: invasive pneumococcal disease, AOM: acute otitis media 4
Risk group/Condition

Children without immunocompromising conditions

Chronic heart disease†

Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions)

Chronic liver disease

Chronic lung disease (including moderate persistent or severe persistent asthma)

Diabetes mellitus

Cerebrospinal fluid leak

Cochlear implant

Children with immunocompromising conditions

On maintenance dialysis or nephrotic syndrome

Congenital or acquired asplenia, or splenic dysfunction

Congenital or acquired immunodeficiency¶

Diseases and conditions treated with immunosuppressive drugs or radiation therapy**

HIV infection

Sickle cell disease or other hemoglobinopathies

Solid organ transplant

† Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.

¶

Includes B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).

** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease. 5
Risk group/Condition

Children without immunocompromising conditions

Chronic heart disease†

Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions)

Chronic liver disease

Chronic lung disease (including moderate persistent or severe persistent asthma)

Diabetes mellitus

Cerebrospinal fluid leak

Cochlear implant

Children with immunocompromising conditions

On maintenance dialysis or nephrotic syndrome

Congenital or acquired asplenia, or splenic dysfunction

Congenital or acquired immunodeficiency¶

Diseases and conditions treated with immunosuppressive drugs or radiation therapy**

HIV infection

Sickle cell disease or other hemoglobinopathies

Solid organ transplant

† Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.

¶

Includes B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).

** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease. 6
Risk group/Condition

Children without immunocompromising conditions

Chronic heart disease†

Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions)

Chronic liver disease

Chronic lung disease (including moderate persistent or severe persistent asthma)

Diabetes mellitus

Cerebrospinal fluid leak

Cochlear implant

Children with immunocompromising conditions

On maintenance dialysis or nephrotic syndrome

Congenital or acquired asplenia, or splenic dysfunction

Congenital or acquired immunodeficiency¶

Diseases and conditions treated with immunosuppressive drugs or radiation therapy**

HIV infection

Sickle cell disease or other hemoglobinopathies

Solid organ transplant

† Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.

¶

Includes B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).

** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease. 7
Rationale for updating indications for risk-based 

recommendations

▪ Improve harmonization between pediatric and adult recommendations

▪ Data supporting increased risk of pneumococcal disease in this population

• Increased pneumococcal pneumonia1 or IPD1,2 risk in children with 

asthma without long-term oral corticosteroid use

• Increased risk of IPD in children with chronic kidney disease 

(regardless of stage)2,3

• Increased pneumococcal pneumonia2 or IPD2,4 risk in children with 

chronic liver disease

IPD=invasive pneumococcal disease

1. Talbot et al. NEJM 2005. Long-term oral corticosteroid use of ≥120 days defined as high risk

2. Pelton et al. CID 2014. Long-term oral corticosteroid use of ≥30 days defined as severe asthma

3. Hjuler et al. Pediatrics 2008. 

4. Van Hoek et al. Journal of Infection 2012
Evidence to Recommendations (EtR) framework

EtR Domain Question

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?

• What is the overall certainty of this evidence for the critical outcomes?

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 outcomes?

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?9
Evidence to Recommendations (EtR) framework

EtR Domain Question

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?

• What is the overall certainty of this evidence for the critical outcomes?

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 outcomes?

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?10
EtR Domain: Public Health Problem
Pneumococcal disease epidemiology in children

• Use of PCVs (PCV7, PCV13) significantly decreased the incidence of 

pneumococcal disease in U.S. children.

• Outpatient ARIs caused by pneumococcus, such as AOM, sinusitis, and 

pneumonia, are common causes of outpatient visits and antibiotic prescribing. 

• Estimated incidence of outpatient visits and antibiotic prescriptions 

attributable to PCV20, non-PCV13 serotypes: 4–5 times PCV15, non-PCV13

• In 2018–2019, the proportion of IPD caused by vaccine serotypes was:

• PCV20, non-PCV13: ~30% of IPD

• PCV15, non-PCV13: ~15% of IPD

• PPSV23, non-PCV20: 1–5% of IPD

• Risk of pneumococcal disease remains high in children with underlying 

conditions that increase the risk of pneumococcal disease.

AOM=acute otitis media; ARI= acute respiratory illness; IPD=invasive pneumococcal disease 

Gierke. February 2023 ACIP meeting presentation

King. February 2023 ACIP meeting presentation 12
Monthly IPD rates (per 100,000) among children aged 

<5 years old, 2018–2022

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

2018 2019 2020 2021 2022*

IPD=invasive pneumococcal disease

CDC ABCs unpublished data. *2022 estimates are preliminary 13
Public Health Problem

Is pneumococcal disease of public health importance in U.S. 

children? 

□ No 

□ Probably no

□ Probably yes

□ Yes

□ Varies

□ Don’t know

14
EtR Domain: Benefits and Harms
Summary of evidence: Benefits, children <2 years 

• Informed by 2 randomized controlled trials (Phase II and III)1,2

• Healthy children randomized to either PCV13 or PCV20

• PCVs given using 3+1 schedule

• Summary of findings

•PCV20 had numerically lower IgG geometric mean concentrations vs. PCV13 

for the 13 shared serotypes

•Post dose 3: 

•PCV20 did not meet noninferiority criteria* vs. PCV13 for serotypes 1, 3, 4, 9V, 23F, and 

12F*** for one of the outcomes 

•Post dose 4: 

•PCV20 noninferior** to PCV13 for all 13 shared serotypes 

•PCV20 noninferior to PCV13*** for all 7 additional serotypes

*Measured as lower bound of 2-sided 95% CI for percent difference proportion of participants (PCV20-PCV13) meeting IgG threshold value of >=0.35μg/mL for all serotypes except ≥ 

0.23 μg/mL, ≥ 0.10 μg/mL and ≥ 0.12μg/mL for serotypes 5, 6B and 19A respectively

**Measured as lower bound of 2-sided 95% CI for IgG geometric mean concentration ratio (PCV20/PCV13) >0.5 

***Compared with the serotype with lowest immune response among PCV13 serotypes except for serotype 3

1. Senders et al. PIDJ 2021

2. Pfizer unpublished data from B7471011 16
Summary of evidence: Safety, children <2 years 

• Serious adverse events (SAEs) across 3 studies (dose 1 through 6 months after 

dose 4)1-3:

• PCV20: 4.5% (101 of 2,232) vs PCV13: 3.7% (64 of 1,717)

• None were considered to be vaccine-related

1. Senders et al. PIDJ 2021

2. Pfizer B7471011, https://www.fda.gov/media/149987/download

3. Pfizer B7471013, https://www.fda.gov/media/149987/download 17
Should PCV20 be recommended as an option for pneumococcal conjugate 

vaccination according to currently recommended dosing and schedules, for U.S. 

children aged <2 years?

Type Outcome Importance

Included in 

evidence profile

Certainty of 

evidence

Benefits

VT-IPD Critical Yes Moderate

VT-pneumonia Critical Yes Moderate

VT-AOM Critical Yes Moderate

VT-pneumococcal 

deaths Critical Yes Moderate

Harms SAEs following 

vaccination Critical Yes Moderate

AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 18
Summary of evidence: 

Benefits, children 2–18 years with underlying conditions 

• No studies conducted among children with underlying medical conditions

• Informed by 1 non-randomized trial (Phase III), no comparator

• Healthy children aged 15 months to 17 years received a dose of PCV20

• Children aged <5 years received ≥3 doses of PCV13

• Summary of findings

• PCV20 was immunogenic* for all 20 vaccine serotypes 1 month after 

vaccination vs. pre-vaccination. 

*Measured as IgG GMCs and GMFR and OPA GMFRs

Pfizer unpublished data from B7471014 19
Summary of evidence: 

Safety, children 2–18 years with underlying conditions

• Serious adverse events (SAEs) :

• PCV20: 0.6% (5/831) 

• None were considered to be vaccine-related

Pfizer unpublished data from B7471014

20
Should PCV20 without PPSV23 be recommended as an option for pneumococcal 

vaccination for U.S. children aged 2–18 years with underlying medical conditions that 

increase the risk of pneumococcal disease?

Type Outcome Importance

Included in evidence 

profile Certainty of evidence

Benefits

VT-IPD Critical Yes Very Low

VT-pneumonia Critical Yes Very Low

VT-AOM Critical Yes Very Low

VT-pneumococcal 

deaths Critical Yes Very Low

Harms SAEs following 

vaccination Critical Yes Very Low

AOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 21
□ Minimal

□ Small

□ Moderate

□ Large

□ Varies

□ Don’t know

Benefits and Harms

How substantial are the desirable anticipated effects?

▪ Routine PCV20 use for children aged <2 years

▪ PCV20 without PPSV23 for children aged 2–18 years with underlying conditions 

• PCV20 provides the broadest serotype coverage among available 

PCVs.

• Unknown how substantial the protection conferred from PCV20 will 

be based on available data. 

• No PCV20 data among children with underlying medical conditions.

22
Benefits and Harms

How substantial are the undesirable anticipated effects?

▪ Routine PCV20 use for children aged <2 years

▪ PCV20 without PPSV23 for children aged 2–18 years with underlying conditions 

□ Minimal

□ Small

□ Moderate

□ Large

□ Varies

□ Don’t know

23
Benefits and Harms

Do the desirable effects outweigh the undesirable effects?

▪ Routine PCV20 use for children aged <2 years

▪ PCV20 without PPSV23 for children aged 2–18 years with underlying conditions 

□ Favors intervention*

□ Favors current recommendation

□ Favors both

□ Favors neither

□ Varies

□ Don’t know

*Intervention: PCV20 use

Comparison: 

• Children <2 years: PCV13 or PCV15 use

• Children 2–18 years with underlying 

conditions: PPSV23 use after currently 

recommended PCV (PCV13 or PCV15) 

doses

24
EtR Domain: Equity
Summary of evidence 

• Disparities in pneumococcal vaccine coverage by race/ethnicity, insurance coverage, 

and poverty level exist1

• Nationally representative PPSV23 vaccine coverage data among children with 

indications are limited2–5

• Range ~20–60%, many reports from single institution 

• Disparities in IPD rates by race and the percentage of census tract poverty remain6,7

• Most of the remaining disparities were due to serotypes not included in PCV20

1. ChildVaxView Interactive Child Vaccination Coverage | CDC

2. Reeves et al. Pediatric Blood & Cancer, 2018

3. Tran et al. Frontiers in Pediatrics, 2021

4. Mirza et al. The Ochsner Journal, 2022

5. Harris et al. Pediatrics, 2022

6. Farrar February 2022 ACIP meeting presentation

7. Kobayashi February 2023 ACIP meeting presentation

26
Equity

What would be the impact of recommending PCV20 for U.S. 

children on health equity?

□ Reduced

□ Probably reduced

□ Probably no impact

□ Probably increased

□ Increased

□ Varies 

□ Don’t know 

27
Equity

What would be the impact of recommending PCV20 for U.S. 

children aged <2 years on health equity?

Probably reduced:

• New interventions are likely to be accessible to wealthy communities, first 

→VFC program mitigates inequities in access to recommended vaccines 

Probably no impact:

• Remaining disparities in vaccine-type disease seem to be minimal 

Probably increased:

• Post-PCV13 data showed that PCV13 reduced disparities in vaccine-type disease 

VFC=Vaccines for Children 28
Equity

What would be the impact of recommending PCV20 without 

PPSV23 for U.S. children aged 2–18 years with underlying 

medical conditions on health equity?

Probably no impact:

• Risk-based recommendation is less likely to be equitable compared with routine 

vaccine recommendations. 

Probably increased:

• PCV20 use without PPSV23 could simplify the pneumococcal vaccine 

recommendations and improve vaccine coverage. 

29
EtR Domain: Values and Preferences
Values and Preferences

Criterion 1: Does the target population feel that the desirable 

effects from vaccination are large relative to undesirable effects?

▪ Routine PCV20 use for children aged <2 years

• Probably Yes

▪ PCV20 without PPSV23 for children aged 2–18 years with 

underlying conditions

• Probably Yes/Yes

31
Values and Preferences

Criterion 2: Is there important uncertainty about, or variability 

in, how much people value the main outcomes?

• Routine PCV20 use for children aged <2 years

• Probably important/not important uncertainty or 

variability

• PCV20 without PPSV23 for children aged 2–18 years with 

underlying conditions

• Probably not important uncertainty or variability

32
Values and Preferences

Uncertainties:

▪ No data assessing the public’s perception of PCV20

▪ No data assessing efficacy/effectiveness of PCV20 against disease

▪ Benefits from PCV20 use alone without PPSV23 for children with 

underlying conditions are uncertain

Probably not important uncertainty or variability:

▪ >90% vaccine coverage for ≥3 PCV doses in children by age 24 months1

▪ Increased cases of invasive pneumococcal disease (late 2022): caregivers of 

the child will likely value the use of PCV20

1. Hill et al. MMWR 2023. 33
EtR Domain: Acceptability
Three healthcare provider surveys

▪ Web-based surveys among providers who administer pneumococcal 

vaccines to children

• 1 by Pfizer (manufacturer of PCV13 and PCV20)1

• 2 by Merck (manufacturer of PCV15 and PPSV23)2,3

1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.

2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.

3. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023. 35
Key findings (Pfizer survey)

Vaccine profiles of PCV15 and PCV20 shown, emphasizing IPD serotype coverage.

Children aged <2 years with incomplete series:

▪ 76% of providers responded that they would transition patients who started their PCV 

series with either PCV13 or PCV15 to PCV20

• To provide protection against as many serotypes as possible (94%). 

Children with underlying conditions:

▪ 43% of providers responded that PCV20 alone without PPSV23 should be 

recommended.

• Prefer/store only 1 vaccine instead of multiple vaccines (61%).

• Prefer conjugated vaccines over unconjugated polysaccharide vaccines (48%). 

1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.

36
Key findings (Merck surveys)

▪ Importance of pneumococcal vaccination

• >90% of providers believed that it is important to administer 

pneumococcal vaccines to children aged <2 years.1

▪ Important vaccine attributes

• ≥90% of providers believed that it is important to have product-specific 

data for immunocompromised or premature children.1

• Of the five vaccine attributes assessed for hypothetical vaccines, immune 

response for the serotypes covered in PCV13 was given the highest 

importance.2

1. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023..

2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023. 37
Acceptability

Is recommending PCV20 acceptable to key stakeholders?

▪ Routine PCV20 use for children aged <2 years

• Yes

▪ PCV20 without PPSV23 for children aged 2–18 years with 

underlying conditions

• Probably Yes/Yes

• Simplifies storage, less prone to vaccine administration errors

• Some providers may not feel comfortable recommending PCV20 alone without 

PPSV23

38
EtR Domain: Resource Use
Summary of evidence

• Routine PCV20 use vs. PCV13 or PCV15 in children aged <2 years

• Base case ranged from cost-saving to $125,000 per QALY gained

• Differences across models related to indirect effects on adult disease

• PCV20 alone without PPSV23 use in children aged 2–18 years with underlying 

conditions

• PCV20 alone instead of PCV13/PCV15+PPSV23* was found to be cost-saving 

in most model scenarios

• Addition of PPSV23 to PCV20 had high cost per QALY gained

• Greater than $1.9 million per QALY gained among CMC

• Between $200,000 to $690,000 per QALY gained among IC

CMC=chronic medical conditions, including chronic heart, lung, and liver disease, diabetes

IC=immunocompromising conditions, including chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV, 

Hodgkin disease, leukemia, lymphoma, solid organ transplants, cochlear implants, CSF leaks, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies

QALY= quality-adjusted life-years

*CMC received 1 dose of PPSV23, IC received 2 doses of PPSV23

40
□ No 

□ Probably no

□ Probably yes

□ Yes

□ Varies

□ Don’t know

Resource Use

Is the option a reasonable and efficient allocation of resources?

▪ Routine PCV20 use for children aged <2 years

▪ PCV20 without PPSV23 for children aged 2–18 years with underlying conditions 

Yes:

• Protects against more pneumococcal serotypes.

Minority opinion:

• Expensive vaccine.

• Uncertainties in the effectiveness remain.

• Only immunogenicity data.

• No PCV20 data from children with underlying conditions.

• Challenging to interpret cost-effectiveness analyses findings that 

use different methods and assumptions (routine PCV20 use).

• Sensitive to launch price.

41
EtR Domain: Feasibility
□ No 

□ Probably no

□ Probably yes

□ Yes

□ Varies

□ Don’t know

Feasibility

Is recommending PCV20 feasible to implement?

▪ Routine PCV20 use for children aged <2 years

▪ PCV20 without PPSV23 for children aged 2–18 years with underlying conditions 

Routine PCV20 use for children aged <2 years:

• PCVs have been recommended for >20 years.

PCV20 without PPSV23 for children with underlying conditions:

• Simpler, streamlined recommendation.

• More feasible in general and are more likely to be followed in 

clinical practice.

43
EtR Domains PCV20, <2 years (routine) PCV20, 2–18 years old 

Public Health Problem Yes

Benefits and Harms

a. Benefits Moderate

b. Harms Minimal

c. Benefit>Harm? Favors intervention/Favors both (split)

d. Overall certainty: effectiveness 2 (moderate) 4 (very low)

e. Overall certainty: safety 2 (moderate) 4 (very low)

Values

a. Desirable>Undesirable? Probably yes Probably yes/yes (split)

b. Uncertainty? Probably important uncertainty or 

variability/Probably no important uncertainty or 

variability (split)

Probably no important uncertainty or variability

Acceptability Yes Probably yes/yes (split)

Resource Use Yes

Equity Probably increased (different opinions)

Feasibility Yes

Summary of Work Group Interpretation of the EtR Domains (Updated)

44
Summary: Work Group Interpretations

Should PCV20 be recommended as an option for pneumococcal conjugate 

vaccination according to currently recommended dosing and schedules for 

U.S. children aged <2 years? 

Comparison: PCV13 or PCV15 

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
Summary: Work Group Interpretations

Should PCV20 be recommended as an option for pneumococcal conjugate 

vaccination according to currently recommended dosing and schedules for 

U.S. children aged <2 years? 

In support of recommending PCV20:

• Additional serotypes covered by PCV20 are expected to prevent additional disease.

In support of recommending both PCV20 and PCV15*:

• We only have immunogenicity study data for both PCV20 and PCV15, clinical 

implications are unknown.

• Range in cost-effectiveness analysis findings. 

• Good to have options for PCVs, in case of challenges with/delays in access to PCV20.

*PCV13 expected to be removed from market after a transition period
Summary: Work Group Interpretations

Should PCV20 without PPSV23 be recommended as an option for children 

aged 2–18 years with underlying medical conditions that increase the risk 

of pneumococcal disease?

Comparison: PCV13 or PCV15 + PPSV23 according to current dosing 

/schedule 

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
Summary: Work Group Interpretations

Should PCV20 without PPSV23 be recommended as an option for children 

aged 2 to 18 years with underlying medical conditions that increase the 

risk of pneumococcal disease?

In support of recommending PCV20 without PPSV23:

• Simplicity of PCV20 use without PPSV23, ease of vaccine storage.

• Immunologic advantages of PCVs over PPSV23.

• PCV20 provides the broadest serotype coverage among available PCVs.

In support of recommending BOTH PCV20 without PPSV23 AND PCV15* + PPSV23:

• No data on PCV20 use in children with underlying medical conditions.

• Harmonization with the updated adult pneumococcal vaccine recommendations 

(October 2022 ACIP meeting).

*PCV13 expected to be removed from market after a transition period
Proposed Policy Options for a Vote
1. Routine PCV use for all children aged <24 months

Use of either PCV15 or PCV20 is recommended for all children aged 2–23 

months according to currently recommended PCV dosing and schedules. 

50
Age at visit/

Health status

No. of previous PCV13/PCV15/PCV20 

doses received Recommended PCV15/PCV20 regimen†

All children (healthy and those with risk conditions)

2–6 mos 1

3 additional doses: 2 doses, 8 wks apart; last dose at age 

12–15 mos

2

2 additional doses: 1 dose 8 wks after most recent dose; 

last dose ≥8 wks later at age 12–15 mos

3 1 additional dose at age 12–15 mos

7–11 mos

1 or 2 (at age <7 mos) 2 additional doses: 1 dose 8 wks after most recent dose; 

last dose ≥8 wks later at age 12–15 mos

3 (at age <7 mos) 1 additional dose at age 12–15 mos

1 (at age ≥7 mos) 2 additional doses: 1 dose 8 wks after most recent dose; 

last dose ≥8 wks later at age 12–15 mos

2 (at age ≥7 mos) 1 additional dose at age 12–15 mos

12–23 mos 1 (at age <12 mos)

2 additional doses: 1 dose ≥8 wks after most recent dose; 

last dose ≥8 wks later

2 or 3 (at age <12 mos) 1 additional dose, ≥8 wks after most recent dose

1 (at age ≥12 mos) 1 additional dose, ≥8 wks after most recent dose†

† Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between doses is 4 weeks.

51
2. Catch-up PCV doses for children aged 24–71 months 

with an incomplete PCV vaccination status

For healthy children aged 24–59 months or through age 71 months 

for children with any underlying condition that increases the risk of 

pneumococcal disease (hereafter, risk condition)* with an incomplete 

PCV vaccination status, use of either PCV15 or PCV20 according to 

currently recommended PCV dosing and schedules is recommended. 

*Risk conditions include: cerebrospinal fluid leak; chronic heart disease; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persistent asthma); cochlear implant; diabetes mellitus; 

immunocompromising conditions (on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired 

immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin disease, and 

solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).

52
Risk group/Condition

Children without immunocompromising conditions

Chronic heart disease†

Chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions)

Chronic liver disease

Chronic lung disease (including moderate persistent or severe persistent asthma)

Diabetes mellitus

Cerebrospinal fluid leak

Cochlear implant

Children with immunocompromising conditions

On maintenance dialysis or nephrotic syndrome

Congenital or acquired asplenia, or splenic dysfunction

Congenital or acquired immunodeficiency¶

Diseases and conditions treated with immunosuppressive drugs or radiation therapy**

HIV infection

Sickle cell disease or other hemoglobinopathies

Solid organ transplant

† Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.

¶

Includes B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).

** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease. 53
Age at visit/

Health status

No. of previous PCV13/PCV15/PCV20 

doses received Recommended PCV15/PCV20 regimen†

Healthy Children

24–59 mos No previous doses or any incomplete 

schedule by 24 mos

1 additional dose, ≥8 wks after most recent dose

5–18 yrs No previous doses or any incomplete 

schedule by 24 mos

No additional dose

Children with risk conditions

24–71 mos No previous doses or any incomplete 

schedule and <3 doses by age 24 mos

2 doses: 1 dose ≥8 wks after most recent dose; last 

dose ≥8 wks later

3 (all at age <12 mos) 1 additional dose, ≥8 wks after most recent dose

† Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between doses is 4 weeks.

54
3. Children aged 2–18 years with any risk condition who have 

completed their recommended PCV doses before age 6 years

For children aged 2–18 years with any risk condition who have 

received all recommended doses before age 6 years

• Using ≥1 dose of PCV20: No additional doses of any pneumococcal 

vaccine are indicated. This recommendation may be updated as 

additional data become available. 

• Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using 

previously recommended doses and schedule is recommended. 

55
Children aged 2–18 years with CMC, CSF leak, or cochlear implant 

who have received all recommended PCV doses before age 6 years, 

current recommendations

CMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persistent or severe persistent asthma), 

diabetes mellitus; CSF=cerebrospinal fluid

PPSV23 Complete with 

either PCV13/15

≥8 weeks

56
Children aged 2–18 years with CMC, CSF leak, or cochlear implant 

who have received all recommended PCV doses before age 6 years, 

proposed recommendations

CMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persistent or severe persistent asthma), 

diabetes mellitus; CSF=cerebrospinal fluid

PPSV23

Complete with ≥8 weeks

either PCV13/15

PCV20

Complete with 

any PCV20 dose

Scenario 1

PCV vaccination status

No additional doses 

indicated

Option 1

Scenario 2

≥8 weeks

Option 2

57
Children with an immunocompromising condition aged 2–18 years 

who have completed PCV doses before age 6 years, current 

recommendations

IC= immunocompromising condition

PPSV23 PPSV23

≥5 years

Complete with 

either PCV13/15 ≥8 weeks

58
Children with an immunocompromising condition aged 2–18 years 

who have completed PCV doses before age 6 years, proposed 

recommendations

IC= immunocompromising condition

PPSV23

≥8 weeks

PCV20

Complete with 

any PCV20 dose

PPSV23

≥5 years

Scenario 1

PPSV23

≥8 weeks

Complete with 

either PCV13/15 ≥5 years

PCV20

≥8 weeks

Option 3

Option 1

Option 2

No additional doses 

indicated

Scenario 2

PCV vaccination status

No additional doses 

indicated

59
4. Children aged 6–18 years with any risk condition 

who have not received any dose of PCV

For children aged 6–18 years with any risk condition who have not 

received any dose of PCV13, PCV15, or PCV20, a single dose of PCV15 

or PCV20 is recommended at least 8 weeks after the most recent dose 

of pneumococcal vaccine. When PCV15 is used, it should be followed 

by a dose of PPSV23 at least 8 weeks later if not previously given. 

60
Current risk-based pneumococcal vaccine recommendations for PCV 

unvaccinated children aged 6–18 years with risk conditions

PCV13/15 recommended

PPSV23 

Recommended

Single PPSV23 revaccination 

5 yrs after first dose

Chronic heart disease Y

Chronic lung disease Y

Diabetes mellitus Y

Cerebrospinal fluid leak Y Y

Cochlear implant Y Y

Chronic renal failure or 

nephrotic syndrome

Y Y Y

Congenital or acquired 

asplenia, or splenic 

dysfunction

Y Y Y

Congenital or acquired 

immunodeficiency

Y Y Y

Diseases and conditions 

treated with 

immunosuppressive drugs or 

radiation therapy

Y Y Y

HIV infection Y Y Y

Sickle cell disease or other 

hemoglobinopathies

Y Y Y

Solid organ transplant Y Y Y
Proposed risk-based pneumococcal vaccine recommendations for 

PCV unvaccinated children aged 6–18 years with risk conditions

PCV15/20 recommended PPSV23 Recommended

Chronic heart disease Y Only if PCV15 used

Chronic kidney disease Y Only if PCV15 used

Chronic liver disease Y Only if PCV15 used

Chronic lung disease* Y Only if PCV15 used

Diabetes mellitus Y Only if PCV15 used

Cerebrospinal fluid leak Y Only if PCV15 used

Cochlear implant Y Only if PCV15 used

Maintenance dialysis or nephrotic syndrome Y Only if PCV15 used

Congenital or acquired asplenia, or splenic 

dysfunction

Y Only if PCV15 used

Congenital or acquired immunodeficiency Y Only if PCV15 used

Diseases and conditions treated with 

immunosuppressive drugs or radiation 

therapy

Y Only if PCV15 used

HIV infection Y Only if PCV15 used

Sickle cell disease or other 

hemoglobinopathies

Y Only if PCV15 used

Solid organ transplant Y Only if PCV15 used

*including moderate persistent or severe persistent asthma
Clinical Guidance
PCV13 use for children aged <6 years

• If only PCV13 is available when the child is scheduled to receive a PCV, 

PCV13 may be given as previously recommended.

• If a child started the PCV series with PCV13, the child may complete the 

series with PCV15 or PCV20 without giving additional doses. The PCV 

series does not need to be restarted. 

64
Children aged 6–18 years with a risk condition who 

have received PCV13 only

For children who have previously received PCV13 only, either a dose of

PCV20 at least 8 weeks later or PPSV23 based on previous dosing and

schedules is recommended.

65
Children who have received hematopoietic stem cell 

transplant (HSCT)

Children who received HSCT are recommended to receive three doses of PCV20, 4 weeks 

apart starting 3–6 months after HSCT. A fourth PCV20 dose is recommended at least 6 

months after the third PCV20 dose, or at least 12 months after HSCT, whichever is later. 

HSCT recipients who have started their pneumococcal vaccine series with PCV13 or PCV15 

may complete their 4-dose pneumococcal vaccine series with PCV20 without giving extra 

doses. 

If PCV20 is not available, three doses of PCV15, followed by a dose of PPSV23 at least 

12 months after HSCT may be given. For patients with chronic graft-versus-host disease 

who are receiving PCV15, a fourth dose of PCV15 can be given in place of PPSV23 since 

these children are less likely to respond to PPSV23. 

A patient’s clinical team is best positioned to determine the appropriate timing of 

vaccination. 

Language aligned with clinical guidance for adults (October 2022 ACIP meeting)

66
Acknowledgements

• ACIP and the Pneumococcal Vaccines Work Group

• CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko, 

Lindsay Zielinski, Emma Accorsi, Adam Cohen, Alison Albert, Angela Jiles, Noele 

Nelson, Diepreye Ayabina, Andrew Leidner, Pedro Moro, Elizabeth Velazquez, 

Marc Fischer, Katie Hamilton, Noelle Sobotka, Rebecca Morgan, Doug CamposOutcalt

67
Summary of voting language:

No change in PCV doses or schedule

1. Use of either PCV15 or PCV20 is recommended for all children aged 2–23 

months according to currently recommended PCV dosing and schedules. 

2. For healthy children aged 24–59 months or through age 71 months for children 

with any underlying condition that increases the risk of pneumococcal disease 

(hereafter, risk condition)* with an incomplete PCV vaccination status, use of 

either PCV15 or PCV20 according to currently recommended PCV dosing and 

schedules is recommended. 

*Risk conditions include: cerebrospinal fluid leak; chronic heart disease; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in 

immunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persistent asthma); cochlear implant; diabetes mellitus; 

immunocompromising conditions (on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired 

immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin disease, and 

solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).

68
Summary of voting language:

Modifications to schedule

3. For children aged 2–18 years with any risk condition who have received all 

recommended doses before age 6 years

• Using ≥1 dose of PCV20: No additional doses of any pneumococcal vaccine are 

indicated. This recommendation may be updated as additional data become available. 

• Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using previously 

recommended doses and schedule is recommended. 

4. For children aged 6–18 years with any risk condition who have not received any dose 

of PCV13, PCV15, or PCV20, a single dose of PCV15 or PCV20 is recommended at least 8 

weeks after the most recent dose of pneumococcal vaccination. When PCV15 is used, it 

should be followed by a dose of PPSV23 at least 8 weeks later if not previously given. 

69
Supplementary Slides

GRADE Summary of Evidence
Search strategy: PCV20 use in children

Database Strategy

No. 

identified

Included in 

GRADE

Clinicaltrials.gov Inclusion: Relevant Phase 2, or 3 randomized controlled trials of PCV20

• Involved human subjects

• Reported primary data

• Included infants and children (age ≤18 years)

• Included data relevant to the efficacy or effectiveness or immunogenicity and safety 

outcomes being measured

• Included data for the dosage and timing being recommended:

o 3+1 series for infants starting the vaccine series as currently recommended

o Catch-up vaccine schedule for older infants and children who did not start the 3+1 series 

in time

o Use of PCV20 to complete the PCV13 series

o Use of PCV20 in series with PPSV23 in older children with underlying conditions in series 

with PPSV23

12 3*

Pubmed

Medline

“PCV20” or “20-valent pneumococcal conjugate vaccine” 

Included studies using the criteria listed above

62 1

Additional 

resources

Unpublished and other relevant data by consulting with the vaccine manufacturer

2 3*

*Same trials. Unpublished data from these trials were obtained from pharmaceutical companies. 71
Included Studies: Routine PCV20 Use in Children Aged <2 years

Author, year Study 

design Intervention Country Age 

Total 

population

N 

Intervention

N 

comparison Outcomes

Funding 

source

Senders, 

2021

Phase II RCT 

in healthy 

full-term 

infants

PCV20 @ 2, 4, 6, 

and 12 months of 

age

US

42–98 

days of 

age at 

consent

460 232 228

Immunogenicity and 

safety

Pfizer

B7471011

Phase III RCT 

in healthy 

full-term 

infants

PCV20 @ 2, 4, 6, 

and 12 – 15 

months of age

US, 

Puerto 

Rico

42–98 

days of 

age at 

consent

1998 1001 997

Immunogenicity and 

safety

Pfizer

B7471013

Phase III RCT 

in healthy 

infants

PCV20 @ 2, 4, 6, 

and 12 – 15 

months of age

US, 

Puerto 

Rico, 

Canada, 

Chile, 

Argentin

a, EU

42–98 

days of 

age at 

consent

1511 1000 551 Safety Pfizer

RCT=Randomized Controlled Trial

72
GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years

Certainty assessment No of patients Results

No of Certainty Importance

studies

Study 

design

Risk of 

bias Inconsistency Indirectness Imprecision Other 

considerations Intervention comparison Relative(95% CI)

Absolute

(95% CI)

Vaccine effectiveness

2

1-2 RCT

Not 

serious Not serious Seriousa Not serious Not serious 921-1022 910-989

• PCV20 had numerically lower 

immune responses compared 

with PCV13 for most of the 13 

shared serotypes.

• PCV20 did not meet one of the 

noninferiority endpointsbfor 

some serotypes (1, 3, 4, 9V, 23F, 

and 12F) after dose 3.

• PCV20 noninferiorcto PCV13 for 

all 13 shared serotypes after 

dose 4. 

• PCV20 noninferiorcto PCV13 for 

all 7 additional serotypes after 

dose 4.

Moderate Critical

RCT=randomized clinical trial

a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.

b. Noninferiority for difference in percentages of participants meeting predefined IgG threshold value was defined as the lower bound of 2-sided 95% confidence interval for percent difference (PCV20-PCV13)>-10%. Additional 7 serotypes contained in 

PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest percentage excluding serotype 3. 

c. Noninferiority for GMC ratio was defined as the lower bound of 2-sided 95% confidence interval of IgG GMC ratio (PCV20/PCV13) >0.5. Additional 7 serotypes contained in PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest 

percentage excluding serotype 3. 

References

1. Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct 

1;40(10):944-951. doi: 10.1097/INF.0000000000003277.

2.B7471011. A Phase 3, Randomized, double-blind trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in healthy infants

73
GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years

Certainty assessment No of patients Results

No of Certainty Importance

studies

Study 

design

Risk of 

bias Inconsistency Indirectness Imprecision Other 

considerations Intervention Comparison Relative(95% CI)

Absolute

(95% CI)

Serious Adverse Events (SAEs) following vaccination

2

1-3 RCT Not 

serious

Not serious Not serious Seriousa Not serious 101/2232

(4.5%)

64/1717

(3.7%)

No vaccine-related 

serious adverse events 

reported

Moderate Critical

RCT=randomized clinical trial

a. No vaccine-related serious adverse events reported

References

1.Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate 

Vaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct 1;40(10):944-951. doi: 10.1097/INF.0000000000003277.

2.B7471011. A Phase 3, Randomized, double-blind trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in healthy infants

3.B7471013. A Phase 3, Randomized, double-blind trial to evaluate the safety of a 20-valent pneumococcal conjugate vaccine in healthy infants. Data limited to U.S. and Puerto Rico sites. 

74
Included Study: PCV20 Use in Children Aged 2–18 Years with Underlying 

Medical Conditions

Author, year Study design Intervention Country Age Total 

population

N 

Intervention

N 

comparison Outcomes

Funding 

source

B7471014

Phase III 

Clinical Trial 

in healthy 

children, 

some 

previously 

vaccinated

Single dose PCV20 

@ 15m to <24m; 

previous 

vaccination ≥3 

doses of PCV13

US

15m 

to 

<24m

209 209 N/A

Immunogenicity

and 

safety

Pfizer

Single dose PCV20 

@ 2y to <5y; 

previous 

vaccination ≥3 

doses of PCV13

2y to 

<5y

216 216 N/A

Single dose PCV20 

@ 5y to <10y

5y to 

<10y

201 201 N/A

Single dose PCV20 

@ 10 to <18y

10y 

to 

<18y

205 205 N/A

75
GRADE Summary of Findings: PCV20 Use in Children Aged 2–18 Years 

with Underlying Medical Conditions

Certainty assessment No of patients Results

No of Certainty Importance

studies

Study 

design

Risk of 

bias Inconsistency Indirectness Imprecision Other 

considerations Intervention comparison Relative(95% CI)

Absolute

(95% CI)

Vaccine effectiveness

1

1 Non-RCT

Very 

Serious

a

Not 

applicable

Very 

Seriousb,c

Not 

serious Not serious 752-757 None

IgG GMCs were higher 1-

month post-PCV20 dose 

compared to before 

vaccination for 13/13 shared 

serotypes and 7/7 additional 

serotypes, for all age groups

Very Low Critical

RCT=randomized clinical trial

a. Study design is an open label non-randomized controlled trial with no comparator group. Downgraded for lack of randomization, lack of blinding, and lack of a comparison group. 

b. Study population did not include children with underlying conditions

c. This is an immunogenicity study and there are no correlates of protection for some critical outcomes considered

References

B7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age

76
GRADE Summary of Findings: PCV20 use in Children Aged 2–18 

Years With Underlying Medical Conditions

Certainty assessment No of patients Results

No of Certainty Importance

studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

PCV20 Intervention Relative

(95% CI)

Absolute

(95% CI)

Serious Adverse Events (SAEs) following vaccination

1

1 Non-RCT Serious

a

Not 

applicable Seriousb Seriousc Not serious 5/831(0.6%) 

No vaccine-related 

SAEs reported Very Low Critical

RCT=randomized clinical trial

a. Study design is an open label non-randomized controlled trial with no comparator group

b. Study population did not include children with underlying conditions

c. No vaccine-related serious adverse events reported; relative risk crossing 1 

Reference

B7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age

77