Skip directly to site content Skip directly to search


Español  Other Languages


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
 Search
		×
			Vaccines site
			Vaccines site
				All CDC
				Submit
			For a full list of topics:A-Z Index
			Advanced Search
		Advanced Search


Advisory Committee on Immunization Practices (ACIP)


Facebook
        Twitter
        LinkedIn
        Syndicate





GRADE: 20-valent pneumococcal conjugate vaccine (PCV20) for adults aged ≥65 yearsGrading of Recommendations, Assessment, Development, and Evaluation										Related Pages
										Introduction
On October 21, 2021, the ACIP recommended use of 20-valent pneumococcal conjugate vaccine (PCV20 [Prevnar 20, Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.]) alone or 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme Corp.]) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) [Pneumovax23, Merck Sharp & Dohme Corp Inc.]) for all adults aged ≥65 years, and for adults aged 19–64 years with certain underlying medical conditions or other risk factors*, who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was employed to guide ACIP’s deliberations regarding use of these vaccines.
**Introduction Footnote**
*Alcoholism, chronic heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear implant, congenital or acquired asplenia, CSF leak, diabetes mellitus, generalized malignancy, HIV, Hodgkin disease, immunodeficiency, iatrogenic immunosuppression, leukemia, lymphoma, multiple myeloma, nephrotic syndrome, solid organ transplants, or sickle cell disease or other hemoglobinopathies.
Methods
A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 and PCV20 among age groups for which the vaccines were approved.  Since only immunogenicity and safety data were available for PCV15 or PCV20, the search included PCV13 and PPSV23 efficacy or effectiveness studies to help interpret PCV15 and PCV20 immunogenicity study findings. Literature search for evidence on both PCV15 and PCV20 was done simultaneously given the similarities in the policy questions and given that use of both PCV15 and PCV20 were considered by the ACIP simultaneously. GRADE assessment was performed for PCV15 and PCV20 studies only. As a basis for the GRADE analysis, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).
Table 1. Policy Question and PICO
Table 1. Policy Question and PICO
Policy question:
**Should PCV20 be routinely recommended to US adults ≥65 years and older?**Population
US adults aged ≥65 yearsIntervention
One dose of PCV20Comparison
1. PCV13 followed by PPSV23 (immunocompromised adults aged ≥65 years)
2. PPSV23 (immunocompetent or healthy adults aged ≥65 years)Outcomes
Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, vaccine-type pneumococcal mortality
Serious adverse events following immunization**Table 1. Footnote**
PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine
Table 2. Outcomes and Rankings
Table 2: Outcomes and Rankings
Outcome
Importance*
Included in evidence profileVaccine-type invasive pneumococcal disease
Critical
YesVaccine-type non-bacteremic pneumococcal pneumonia
Critical
YesVaccine-type pneumococcal mortality
Critical
YesSerious adverse events following immunization
Critical
Yes
**Table 2. Footnote**
*Three options: 1. Critical; 2.  Important but not critical; 3. Not important for decision making
We leveraged a systematic review presented to the World Health Organization Strategic Advisory Group of Experts (SAGE) meeting in October 2020, which included literature up to March 2019 (1). To identify literature published during April 2019 to February 2021, we searched Pubmed, Medline, Embase, CINAHL, Scopus, Epistemonikos and Cochrane library databases. The search terms are included in the **appendix I**. Search results were supplemented by an updated Pubmed search using “V114*”, “PCV15”, “PCV20”. Unpublished data were provided by the vaccine manufacturers.
Studies were included if they presented primary data on PCV20 use in adults aged 50≥ years. Of the 2,499 titles screened for WHO SAGE and 923 titles screened for the updated review in 2021, 1 unpublished and 1 published PCV20 studies were included in the GRADE analysis (2, 3). Characteristics of these studies are presented in **appendix II.** Beneficial and harmful outcomes for the GRADE assessment were selected by the ACIP Pneumococcal Vaccines Work Group calls and via an email survey in which Work Group members were asked to rank the relative importance of each outcome. Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, vaccine-type pneumococcal mortality, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).
**Methods Footnote**
*V114 is the name used for Merck’s investigational 15-valent pneumococcal conjugate vaccine candidate
Table 3a. Summary of Studies Reporting Immunogenicity
Table 3a. Summary of Studies Reporting Immunogenicity
Study
Age or other characteristic of importance
N intervention
N comparison
Comparator vaccine
OPA GMT Ratios* [range (serotype)]
Absolute difference in % seroresponders
(serotype)
Interpretation
Study limitations (Risk of Bias)B7471007
Adults ≥60 years
1435
1420
PCV13
0.76 (6A) to 1.00 (14)
-5.6 (3) to -0.5 (7F)
GMT ratios
PCV20<PCV13 in 12/13 PCV13 serotypes
Noninferiority criteria met for all 13/13 PCV13 serotypes% seroresponders
PCV20<PCV13 in 12/13 serotypes
Significantly lower for 1/12 (3)
Not serious1433
1383
PPSV23
(7 common ST†– PCV13 ST)
0.55 (8) to 3.12 (15B)
-9 (8) to 14 (15B)
GMT ratios
PCV20>PPSV23 in 6/7 serotypes
Noninferiority criteria met for 6/7 serotypes (not met for serotype 8)% seroresponders
PCV20>PPSV23 in 6/7 serotypes (all significant)
PCV20<PPSV23 in 1/7 (significant for serotype 8)Hurley 2020
Adults 60 – 64 years
195-210
194-208
PCV13
0.62 (19F) to 0.90 (6B)
-9.8 (19F) to 1.3 (6A)
GMT ratios
PCV20<PCV13 in 13/13 serotypes
CI did not overlap in 4/13% seroresponders
PCV20<PCV13 in 12/13 shared serotypes (all non-significant)
Not serious185-207
181-204
PPSV23
(7 common ST – PCV13 ST)
0.64 (8) to 2.64 (10A)
-4.9 (8) to 14.7 (10A)
GMT ratios
PCV20>PPSV23 in 6/7 shared serotypes (CI did not overlap in 3/6)
PCV20<PPSV23 in 1/7 shared serotype (serotype 8, CI did not overlap)% seroresponders
PCV20>PPSV23 in 6/7 shared serotypes (significantly higher in 2/6)
PCV20<PPSV23 in 1/7 shared serotype 8 (non-significant)195-204
196-203
PCV13+PPSV23
PCV13 serotypes: 0.50 (3) to 0.78 (6B)
7 common serotypes in addition to PCV13 types: 0.64 (8) to 2.64 (10A)
Data not presented
GMT ratios
PCV20<PCV13+PPSV23 in 13/13 shared serotypes (PCV13 serotypes)
PCV20>PCV13+PPSV23 in 6/7 shared serotypes (additional serotypes in PCV20)
**Table 3a. Footnotes**
CI=confidence interval, GMT=geometric mean titers, OPA=opsonophagocytic activity, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine
*Ratio calculated as [GMT (PCV20)] / [GMT (comparator vaccine)]. Range of GMT ratios for 13 serotypes common to PCV13 and PCV20 is shown†ST: serotype
Table 3b. Summary of Studies Reporting Safety
Table 3b. Summary of Studies Reporting Safety
Study
Age or other characteristic of importance
N intervention
N comparison
Comparator vaccine
Absolute % difference (% SAE PCV20 – % SAE comparator)
N related to vaccine
Study limitations (Risk of Bias)B7471007
Adults ≥60 years
1461
1445
PCV13 or PCV13+PPSV23 (6-month observation period)
0.5
(CI overlaps)
0
Not seriousHurley 2020
Adults 60 – 64 years
221
222
PCV13 (1-month observation period)
-0.5
(CI overlaps)
0
Not serious213
214
PCV13+PPSV23 (12-month study period)
-0.9
(CI overlaps)
0
**Table 3b. Footnotes**
CI=confidence interval, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine, SAE=serious adverse events
Table 4. GRADE Summary of Findings Table
Table 4. GRADE Summary of Findings Table
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies (reference)
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison
Relative effect
Absolute effectVaccine effectiveness (Vaccine-type invasive pneumococcal disease, Vaccine-type non-bacteremic pneumococcal pneumonia, Vaccine-type pneumococcal mortality)**2 (2, 3)**
Randomized studies
Not serious
Not serious
Serious*
Not serious
Not serious
1630 – 1645
1614 – 1628
PCV20 v PCV13: Non-inferiority met for all 13 shared serotypes
PCV20 had slightly lower immune responses vs. PCV13 for all 13 shared serotypes
PCV20 v. PPSV23: Non-inferiority met for 6 of 7 serotypes (not met for serotype 8).
PCV20 had greater immune responses vs. PPSV23 for 6 of 7 shared serotypes.
2
CriticalSerious adverse events**2 (2, 3)**
Randomized studies
Not serious
Not serious
Not serious
Serious†
None
0/1682
0/1687
non estimable
—
2
Critical
**Table 4. Footnotes**
PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine, SAE=serious adverse events
*These are all immunogenicity studies and there are no correlates of protection†No vaccine-related serious adverse events reported; sample size relatively small
Table 5: Summary of Evidence for Outcomes of Interest
Table 5: Summary of Evidence for Outcomes of Interest
Outcome
Importance
Included in profile
CertaintyVaccine-type invasive pneumococcal disease
Critical
Yes
2, moderateVaccine-type non-bacteremic pneumococcal pneumonia
Critical
Yes
2, moderateVaccine-type pneumococcal mortality
Critical
Yes
2, moderateSerious adverse events following immunization
Critical
Yes
2, moderateSummary
The evidence type for use of PCV20 in adults aged ≥65 years was determined to be 2 (moderate certainty of evidence). The ACIP reviewed the results of both GRADE analysis and the Evidence to Recommendations (EtR) framework in June 2021. An updated EtR table was shared with the ACIP in September 2021. In October 2021, the ACIP recommended use of PCV20 for all adults aged ≥65 years who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown.
References
World Health Organization. Strategic Advisory Group of Experts on Immunization 5-7 October 2020. 2020 [cited 2021 July 28]; Available from: https://terrance.who.int/mediacentre/data/sage/SAGE_eYB_October_2020.pdf?ua=1.
Hurley D, Griffin C, Young M, Scott DA, Pride MW, Scully IL, et al. Safety, Tolerability, and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine (PCV20) in Adults 60 to 64 Years of Age. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Jul 27.
Essink B, Sabharwal C, Xu X, Sundaraiyer V, Peng Y, Moyer L, et al. 3. Phase 3 Pivotal Evaluation of 20-valent Pneumococcal Conjugate Vaccine (PCV20) Safety, Tolerability, and Immunologic Noninferiority in Participants 18 Years and Older. Open Forum Infect Dis. 2020;7(Suppl 1):S2-S.Appendix I. Search Strategy
Appendix I. Search Strategy
Database
Strategy
Run Date
Records**Medline
(OVID)**
1. streptococcus pneumoniae/
2. (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”).tw,kf.
3. 1 or 2
4. vaccination/ or immunization/ or Vaccines, Conjugate/
5. (vaccine? or vaccination? or immunisation or immunization).tw,kf.
6. 4 or 5
7. Pneumococcal Vaccines/
8. (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”).tw,kf.
9. 7 or 8
10. (3 and 6)
11. 10 or 9
12. comparative effectiveness research/ or treatment outcome/ or Vaccine Potency/
13. (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”).tw,kf.
14. 12 or 13
15. adult/ or aged/ or “aged, 80 and over”/ or frail elderly/
16. (adult? or elderly or elderlies).tw,kf.
17. 15 or 16
18. 11 and 14 and 17
19. (201904* OR 201905* OR 201906* OR 201907* OR 201908* OR 201909* OR 201910* OR 201911* OR 201912* OR 2020* OR 2021*).ed,ep,yr,dp,dt.
20. 17 and 18
02/18/2021
351**Embase
(OVID)
1988-**
1. Streptococcus pneumoniae/
2. (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”).tw,kw.
3. 1 or 2
4. vaccination/ or immunization/ or vaccine/
5. (vaccine? or vaccination? or immunisation or immunization).tw,kw.
6. 4 or 5
7. Pneumococcus vaccine/
8. (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”).tw,kw.
9. 7 or 8
10. 3 and 6
11. 9 OR 10
12. comparative effectiveness/ or treatment outcome/
13. (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”).tw,kw.
14. 12 or 13
15. aged/ or adult/ or aged hospital patient/ or frail elderly/ or institutionalized elderly/ or very elderly/
16. (adult? or elderly or elderlies).tw,kw.
17. 15 or 16
18. 11 and 14 and 17
19. (201904* OR 201905* OR 201906* OR 201907* OR 201908* OR 201909* OR 201910* OR 201911* OR 201912* OR 2020* OR 2021*).dc
20. limit 19 to (conference abstracts or embase)
02/18/2021
521
–
duplicates
=
unique items**Cochrane Library**
(
(
(pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”):ti,ab
AND
([mh Vaccines] OR [mh Immunization] OR (vaccine# or vaccination# or immunisation or immunization):ti,ab)
)
OR
(MH “Pneumococcal Vaccine”) OR TI (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”) OR AB (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”)
)
AND[mh “Treatment Outcomes”] OR (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”):ti,abAND[mh Adult] OR [mh Aged+] OR (adult# or elderly or elderlies):ti,ab
02/18/2021
56
–
duplicates
=
unique items**CINAHL
(EbscoHost)**
(
(TI (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”) OR AB (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”)) AND ((MH “Vaccines”) OR (MH “Immunization”) OR TI (vaccine# or vaccination# or immunisation or immunization) OR AB (vaccine# or vaccination# or immunisation or immunization))
OR
(MH “Pneumococcal Vaccine”) OR TI (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”) OR AB (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”)
)
AND
(MH “Treatment Outcomes”) OR TI (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”) OR AB (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”)
AND
((MH “Adult”) OR (MH “Aged+”) OR TI (adult# or elderly or elderlies) OR AB (adult# or elderly or elderlies))Limiters – Published Date: 20190401-20210218; Exclude MEDLINE records
02/18/2021
43
–
duplicates
=
unique items**Scopus
(for WOS)**
**(TITLE-ABS-KEY**(“heptavalent” or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or “pcv10” or “pcv 10” or “13valent” or “13 valent” or “pcv13” or “pcv 13” or “ppv23” or “ppv 23” or “23 valent” or “23valent”) OR (**TITLE-ABS-KEY**(“vaccine$” or “vaccination$” or “immunisation” or “immunization”) AND **TITLE-ABS-KEY**(“pneumococcal” or “pneumococci” or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”))) AND**TITLE-ABS-KEY**(“adult$” or “elderly” or “elderlies”) **AND TITLE-ABS-KEY**(“efficacy” or “effectiveness” or “effects” or “immune response” or “impact” or “treatment outcome”)
Limit April 2019 –
02/18/2021
458
–
duplicates
=
unique itemsEpistemonikos
Search 1:
(pneumococcal OR pneumococci OR “streptococcus pneumonie” OR “streptococcus pneumoniae” OR “s pneumoniae”) AND (vaccine* OR vaccination* OR immunisation OR immunization) AND (efficacy OR effectiveness OR effects OR “immune response” OR impact OR “treatment outcome”) AND (adult* OR elderly OR elderlies)
– limited to 2019-2021Search 2:
(heptavalent OR “7 valent” OR “7valent” OR “pcv 7” OR pcv7* OR “10 valent” OR “10valent” OR pcv10 OR “pcv 10” OR “13valent” OR “13 valent” OR pcv13 OR “pcv 13” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”) AND (efficacy OR effectiveness OR effects OR “immune response” OR impact OR “treatment outcome”) AND (adult* OR elderly OR elderlies)
– limited to 2019-2021
02/18/2021
19 + 10
–
duplicates
=
unique items
Appendix II. Studies Included in the Review of Evidence
Appendix II. Studies Included in the Review of Evidence
Study
Study design
Country (or more detail, if needed)
Age
Total population
N Intervention
N comparison
Outcomes
Funding sourceB7471007
Phase III randomized controlled trial (pivotal trial)
US and Sweden
Adults ≥60 years
2855
1435
1420
Immunogenicity,
Safety
Pfizer2816
1433
1383Hurley 2020
Phase II randomized controlled trial
US
Adults 60 – 64 years
389-418
195-210
194-208
Immunogenicity,
Safety
Pfizer366-411
185-207
181-204
Top of Page
							
					
						Page last reviewed:  January 27, 2022					Content source: 	National Center for Immunization and Respiratory Diseases homeACIP Home
Meeting Information
Committee Informationplus icon
Role of the ACIP in CDC’s Vaccine Recommendations
Charter
Economics Studies
Committee Membersplus icon
ACIP Membership Roster
Apply for ACIP Membership
Work Groupsplus icon
VaST Reportsplus icon
June 28, 2021
May 24, 2021
May 17, 2021
March 29, 2021
Recommendationsplus icon
Shared Clinical Decision-Making Recommendations
Evidence Based Recommendationsplus icon
About GRADE
Grade Evidence Tables
Evidence to Recommendations Frameworks Vaccines & ImmunizationsImmunization SchedulesVFC ResolutionsVaccine Information Statements (VISs)
  1600 Clifton Road, N.E., Mailstop A27
Atlanta, GA 30329-4027acip@cdc.gov


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov


Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue