Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): 21-valent Pneumococcal Conjugate Vaccine (PCV21) Use among Adults Aged ≥19 Years Who Currently Have a Recommendation to Receive a Pneumococcal Conjugate Vaccine

About

CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Introduction

On June 27, 2024, the U.S. Advisory Committee on Immunization Practices (ACIP) recommended 21-valent pneumococcal conjugate vaccine (PCV21) as an option for adults aged ≥19 years who currently have a recommendation to receive a dose of pneumococcal conjugate vaccine (PCV). A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for evidence assessment and decision-making informed ACIP’s deliberations regarding use of this vaccine.

Methods

A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV21 among adults. As a basis for the GRADE evidence assessment, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).

We updated a previously published systematic review presented to ACIP in October 2022, which included literature published through March 2022.12 Pubmed, Embase, Cinhal, Web of Science, Epistemonikos, and Cochrane databases were searched to include published literature through September 18, 2023 using search terms listed in Appendix 1. In addition, we conducted an additional Pubmed search on October 17, 2023 using search terms specific to PCV21 and the results were further supplemented by a search of clinicaltrials.gov using "V116", "21-valent pneumococcal conjugate vaccine" or "PCV21" (Appendix 2). Unpublished data from trials identified through clinicaltrials.gov, but not yet publicly available, were provided by the vaccine manufacturers.

Studies were eligible for inclusion into the review if they presented primary data on PCV21 use from phase II or III clinical trials in adults aged ≥19 years. Of the 25 titles identified through the updated Pubmed search and 10 trials identified through clinicaltrials.gov, 6 trials met the inclusion criteria after double-screening of title/abstract and full-text screening. Eligible titles identified through the original search on September 18, 2023 were all captured through the updated Pubmed search in October. Characteristics of these studies are presented in Appendix 3. Outcomes critical and important for decision-making were previously identified by the ACIP Pneumococcal Vaccines Work Group. Work Group members rated and ranked outcomes using a survey, identifying a final list to drive the systematic review (Table 2). Vaccine-type (VT) invasive pneumococcal disease (IPD), VT nonbacteremic pneumococcal pneumonia (NBPP), VT pneumococcal mortality, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).

Tables

Table 1: Policy Question and PICO

Policy question: Should PCV21 be recommended for US adults aged ≥19 years who currently have a recommendation to receive a pneumococcal conjugate vaccine?
Population
  • US adults aged ≥65 years who have never received a pneumococcal conjugate vaccine
  • US adults aged 19-64 years with a risk condition, who have never received a pneumococcal conjugate vaccine
  • US adults aged ≥19 years who have received a pneumococcal conjugate vaccine (PCV7, PCV13, or PCV15), but have not completed the recommended series
Intervention One dose of PCV21 (V116)
Comparison Adults who have not received a pneumococcal conjugate vaccine
  • One dose of PCV15 followed by PPSV23
  • One dose of PCV20

Adults who have received a pneumococcal conjugate vaccine but have not completed the recommended series

  • One dose of PCV20
  • ≥1 dose of PPSV23
Outcomes VT-IPD, VT-NBPP, VT-pneumococcal mortality, serious adverse events
VT: vaccine-type, IPD: invasive pneumococcal disease, NBPP: non-bacteremic pneumococcal pneumonia

Table 2: Outcomes and Rankings

Outcome Importance* Included in evidence profile
VT-IPD Critical Yes
VT-NBPP Critical Yes
VT-pneumococcal mortality Critical Yes
Serious adverse events following immunization Critical Yes

*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making

Table 3: Summary of Studies Reporting Outcomes of Interest

Table 3a. Summary of Studies Reporting Immunogenicity

Study Study design; population and age N of participants, intervention N of participants, comparison Comparator vaccine GMT ratios, range (serotype) Absolute difference in % seroresponders1, range (serotype) Interpretation Study limitations (Risk of Bias)
Platt, Lancet ID 2023 Phase II RCT; US adults ≥50 years 252 254 PPSV23 Shared:
0.94 (33F) to 2.57 (12F)
Unique:
3.00 (15C) to 34.91 (31)		 Shared:
-7.3 (33F) to 740.1 (11A)
Unique:
17.5 (15C) to 67.5 (24F)		 GMT ratios
  • (V116)/(PPSV23) >1 for 9/12 shared serotypes; 95% CI did not cross 1 for 5/9
  • (V116)/(PPSV23) >1 for 9/9 unique serotypes; 95% CI did not cross 1 for all serotypes
  • V116 met non-inferiority criteria2 for 12/12 shared and superiority criteria3 for 9/9 unique serotypes vs. PPSV23

% seroresponders

  • V116 > PPSV23 for 6/12 shared serotypes
  • V116 > PPSV23 for 9/9 unique serotypes
 Low
V116-003 Phase III RCT; adults 18-49 years; pneumococcal vaccine – naïve 184 - 198 550 - 575 PCV21, 50 -64 years 1.09 (3) to 2.10 (31) Not reported GMT ratios
  • (18-49 year olds)/ (50-64 year olds)>1 for all serotypes; 95% CI did not cross 1 except for serotypes3 and 19A
  • All serotypes met criteria for immunobridging4
 Low
Phase III RCT; adults ≥50 years; pneumococcal vaccine – naïve 1145 - 1161 1150 - 1162 PCV20 Shared: 0.76 (19A) to 1.55 (3)
Unique:
2.03 (15C) to 38.70 (24F)		 Unique:
9.2 (15C) to 74.2 (24F)		 GMT ratios
  • (V116 /PCV20)>1 for 6/10 shared serotypes; 95% CI did not cross 1 for 4/6
  • (V116/PCV20)>1 for 11/11 unique serotypes; 95% CI did not cross 1 for all
  • V116 met non-inferiority criteria5 for 10/10 shared and superiority criteria6 for 10/11 unique serotypes (not serotype 15C) vs. PCV20

% seroresponders

  • V116 > PCV20 for 11/11 unique serotypes
  • V116 met superiority criteria7 for 10/11 unique serotypes (not serotype 15C) vs. PCV20
V116-005 Phase III RCT; US adults ≥50 years; 29% prior PCV13 or PPSV23 V116 + QIV (coadministration); 511- 525 458 - 499 QIV + V116 (1 month later) 0.56 (23B) to 0.84 (3) Not reported GMT ratios
  • (V116 coadministered with QIV)/(V116 administered sequentially)<1 for all serotypes; 95% CI did not cross 1 except for serotype 33F
  • V116 coadministered with QIV met non-inferiority criteria8 for 20/21 serotypes (not serotype 23B) vs. sequential administration
 Low
V116-006 Phase III RCT; adults ≥50 years; previous PPSV23 ≥1 year prior to enrollment 175 - 212 91 -114 PCV15 Shared:
0.75 (19A) to 1.27 (33F)
Unique:
1.75 (9N) to 26.7 (31)		 Shared:
-6.2 (19A) to 0.4 (33F)
Unique:
15.5 (9N) to 72.5 (24F)		 GMT ratios
  • (V116)/(PCV15)>1 for 4/6 shared serotypes
  • (V116)/(PCV15)>1 for 15/15 unique serotypes

% seroresponders

  • V116 > PCV15 for 1/6 shared serotypes
  • V116 > PCV15 for 15/15 unique serotypes
 Low
Phase III RCT; adults ≥50 years; previous PCV13 ≥1 year prior to enrollment 125 - 161 58 -76 PPSV23 Shared:
0.67 (3) to 2.21 (10A)
Unique:
2.00 (6A) to 56.6 (24F)		 Shared:
-10.5 (9N) to 19.5 (11A)
Unique:
12.3 (15C) to 77.0 (24F)		 GMT ratios
  • (V116)/(PPSV23)>1 for 7/12 shared serotypes
  • (V116)/(PPSV23)>1 for 9/9 unique serotypes

%seroresponders

  • V116 > PPSV23 for 6/12 shared serotypes
  • V116 > PPSV23 for 9/9 unique serotypes
V116-007 Phase III RCT; Adults ≥18 years living with HIV; 36% prior PCV13 or PPSV23 123 - 137 98 - 130 PCV15 + PPSV23 Shared: 0.82 (19A) to 2.17 (11A)
Unique:
2.30 (15C) to 10.74 (31)		 Shared:
-6.7 (19A) to 12.4 (17F)
Unique:
9.4 (15C) to 57.2 (31)		 GMT ratios
  • (V116+placebo)/(PCV15+PPSV23)>1 for 7/13 shared serotypes
  • (V116+placebo)/(PCV15+PPSV23) for 8/8 unique serotypes

%seroresponders

  • V116 > PCV15+PPSV23 for 8/13 shared serotypes
  • V116 > PCV15+PPSV23 for 8/8 unique serotypes
 Low

CI=confidence interval, GMT=geometric mean titer, QIV=quadrivalent inactivated influenza vaccine, RCT=randomized controlled trial

  1. % seroresponders = proportions of participants with a ≥4-fold rise in serotype-specific OPA responses.
  2. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.
  3. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.
  4. Immunobridging for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 18 to 49 group/V116 50 to 64 group] to be >0.5.
  5. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >0.5.
  6. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.
  7. Superiority for difference in proportions of participants with a ≥4-fold rise in serotype-specific OPA responses from baseline to 30 days postvaccination was defined as the lower bound of the 2-sided 95% CI of the differences [V116 / PCV20] between the proportions of participants with a ≥4-fold rise from baseline to 30 days postvaccination to be >0.1.
  8. Noninferiority for GMT ratio was defined as the lower bound of the 2-sided 95% CI of the OPA GMT ratio (concomitant group/sequential group) to be >0.50.

Table 3b. Summary of Studies Reporting Safety

Study Study Design; population and age N of participants, intervention N of participants, comparison Comparator vaccine Absolute % difference
(% SAE PCV21 – % SAE comparator)		 Number related to vaccine Study limitations (Risk of Bias)
Platt, Lancet ID 2023 Phase II RCT; healthy US adults ≥50 years 254 254 PPSV23 1% 0 Low
V116-003 Phase III RCT; adults ≥50 years; pneumococcal vaccine – naïve 1177 1175 PCV20 -0.4% (-1.6, 0.7) 0 Low
Phase III RCT; adults 18 - 49 years; pneumococcal vaccine – naïve 200 100 PCV20 -2.5% (-8.0, 0.3) 0
V116-004 Phase III RCT; adults 18 – 49 years; pneumococcal vaccine – naïve 1616 541 PPSV23 -0.2% (-1.6, 0.6) 0 Low
V116-005 Phase III RCT; adults ≥50 years; co-administration with quadrivalent influenza vaccine 534 535 Separate administration
(1 month apart)		 -1.3% (-3.4, 0.6) 1* Low
V116-006 Phase III RCT; adults ≥50 years; previous PPSV23 ≥1 year prior to enrollment 230 117 PCV15 -2.5% 1** Low
Phase III RCT; adults ≥50 years; previous PCV13 ≥1 year prior to enrollment 174 85 PPSV23 -2.4% 0
Phase III RCT; adults ≥50 years; previous PCV13+PPSV23, PCV15+PPSV23, PCV15, PCV20, or PPSV23+PCV13 ≥1 year prior to enrollment 105 -- none 1.9% 0
V116-007  Phase III RCT; adults ≥18 years living with HIV; 36% prior PCV13 or PPSV23 155 155 PCV15+PPSV23 -1.3% 0 Low
SAE= serious adverse event
*Bronchospasm (V116-005): 50-year-old female in the sequential group with bronchospasm within 30 minutes after the 2nd vaccination (V116); duration 23 hours; resolved (Merck, WG presentation, Dec 2023)**Injection site cellulitis (V116-006): 67-year-old female in Cohort 1 (prior PPSV23) with injection site cellulitis on Day 6; duration 1.57 weeks; resolved (Merck, WG presentation, Dec 2023)

Table 4 GRADE Summary of Findings Tables

References in this table: 345678

Certainty assessment № of patients Effect Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerationsa PCV21 Comparison Relative
(95% CI)		 Absolute
(95% CI)
VT-IPD, VT-NBPP, VT-pneumococcal mortality outcome (Assessed with: Immunogenicity)
53–7 Randomized studies Not serious Not serious Seriousb Not serious Not serious 123 - 1161 58 - 1162
  • V116 met non-inferiority criteriac for 9/9 shared and superiority criteriad for 12/12 unique serotypes vs. PPSV23
  • V116 met non-inferiority criteriae for 10/10 shared and superiority criteriaf 10/11 unique serotypes vs. PCV20
  • V116 had numerically higher immune responses for 1-4/6 shared and all unique serotypes vs. PCV15
 Moderate Critical
Serious adverse events following immunization
63–8 Randomized studies Not serious Not serious Not serious Seriousg Not serious 57/4445
(1.3%)		 63/2962
(2.1%)		 Absolute % difference for SAEs across studies is -0.8%; two SAEs deemed vaccine-relatedh in the V116 group reported Moderate Critical
  1. Other considerations include publication bias and factors that increase the quality of evidence.
  2. These are all immunogenicity studies and there are no established correlates of protection for the critical outcomes considered.
  3. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.
  4. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.
  5. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >0.5.
  6. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.
  7. Few vaccine-related serious adverse events reported.
  8. Bronchospasm (V116-005): 50-year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116-006): 67-year-old female in Cohort 1 (prior PPSV23) with injection site cellulitis on Day 6; duration 1.57 weeks; resolved (Merck, unpublished).

Table 5: Summary of Evidence for Outcomes of Interest

Outcome Importance Included in profile Certainty
VT-IPD Critical Yes* Moderate
VT-NBPP Critical Yes* Moderate
VT-pneumococcal mortality Critical Yes* Moderate
Serious adverse events following immunization Critical Yes Moderate
*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes

Summary

The certainty of evidence for use of PCV21 for adults aged ≥19 years who currently have a recommendation to receive a dose of PCV was determined to be moderate for VT-IPD, VT-NBPP, and VT-pneumococcal mortality. Assessment on indirectness was downgraded to serious since only immunogenicity studies were available and there are no established correlates of protection for PCV21 against the critical outcomes. The certainty of evidence for SAEs following immunization was determined to be moderate. Assessment on imprecision was downgraded to serious because few vaccine-related serious adverse events were reported in studies with small sample sizes. ACIP reviewed the results of both the GRADE evidence assessment and the Evidence to Recommendations (EtR) framework during February and June 2024 ACIP meetings. On June 27, 2024, ACIP recommended the use of PCV21 as an option for adults aged ≥19 years who currently have a recommendation to receive a dose of PCV.

Appendices

Appendix 1. Studies Included in the Review of Evidence

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. exp adult/
16. (adult? or elderly or elderlies).tw,kf.
17. 15 or 16
18. 11 and 14 and 17

March 2022 - current

 09/18/2023 203
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. exp adult/
16. (adult? or elderly or elderlies).tw,kw.
17. 15 or 16
18. 11 and 14 and 17

March 2022 - current

 9/18/2023 495

-
duplicates

= 315
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 (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,ab

AND

[mh ^Adult] OR (adult# or elderly or elderlies):ti,ab

March 2022 - current

 9/18/2023 21

-
duplicates

= 13
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))

March 2022 - current

 

 9/18/2023 39

-
duplicates

= 8
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")

 

March 2022 - September 2023

 9/18/2023 525

-
duplicates

= 156
unique items
Epistemonikos 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 2022-2023

 

Search 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 2022-2023

 

– limited to 2022-2023

 9/18/2023 111

-
duplicates

= 18
unique items

Appendix 2. Updated Search conducted on October 17, 2023

Database Strategy
clinicaltrials.gov Search terms (searched separately): "V116"; "21-valent pneumococcal conjugate vaccine";"PCV21"
Inclusion: Relevant Phase 2 or 3 randomized controlled trials of PCV21
  • Involved human subjects
  • Reported primary data
  • Included adults (age ≥19 years)
  • Included data relevant to the efficacy or effectiveness or immunogenicity and safety outcomes being measured
Pubmed "V116" or "21-valent pneumococcal conjugate vaccine" or "PCV21"
Included studies using the criteria listed above
Additional resources Unpublished and other relevant data by consulting with vaccine manufacturers and subject matter experts

Appendix 3. Studies Included in the Review of Evidence

Study Study design Country Age Total population N Intervention N comparison Outcomes Funding source
Platt, Lancet ID 2023 RCT (Phase II) US Adults ≥50 years 508 254 PPSV23: 254 Immunogenicity and Safety MERCK
V116-003 RCT (Phase III); pivotal study US, Australia, Belgium, Chile, Germany, Korea, New Zealand, Puerto Rico, Sweden, Taiwan, Turkey Healthy adults ≥50 years, pneumococcal vaccine – naïve 2,663 1,179 PCV20: 1,177 Immunogenicity and Safety MERCK
Healthy adults 18 - 49 years, pneumococcal vaccine – naïve 200 PCV20:  100
V116-004 RCT (Phase III) US, Austria, Canada, Denmark, Finland, Israel, Poland, Spain Adults 18 - 49 years with underlying chronic conditions 2,162 1,617 PPSV23:540 Safety MERCK
V116-005 RCT (Phase III) US Adults ≥50 years 1,080 (V116 + QIV, coadministered): 536 (QIV followed by V116): 536 Immunogenicity and
Safety		 MERCK
V116-006 RCT (Phase III) US, Canada, Israel, France, Italy, Japan, Korea, Spain, Taiwan Adults ≥50 years, previous PPSV23 ≥1 year prior to enrollment 348 229 PCV15, n=119 Immunogenicity
and
Safety		 MERCK
Adults ≥50 years, previous PCV13 ≥1 year prior to enrollment 259 174 PPSV23
N=85
Adults ≥50 years, PCV13+PPSV23, PCV15+PPSV23, PCV15, PCV20, or PPSV23+PCV13 ≥1 year prior to enrollment 105 105 None
V116-007 RCT (Phase III) Belgium,  Chile,  France,  South Africa,
Thailand,
United States		 Adults ≥18 years living with HIV; 36% prior PCV13 or PPSV23* 313 156 PCV15+PPSV23, n=157 Immunogenicity and Safety MERCK
*V116-007: 36 (11.5%) had prior receipt of PCV13 only, 77 (24.7%) had prior receipt of PPSV23 only or prior receipt of PCV13 and PPSV23; 199 (63.8%) were PCV13- and PPSV23-naïve
Print
Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)
  1. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): 20-valent pneumococcal conjugate vaccine (PCV20) use among adults aged ≥65 years who previously received a 13-valent pneumococcal conjugate vaccine (PCV13) | CDC. September 25, 2023. Accessed August 25, 2024. https://www.cdc.gov/vaccines/acip/recs/grade/PCV20-prev-vax-older-adults.html
  2. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): 20-valent pneumococcal conjugate vaccine (PCV20) use among adults aged 19–64 years with an immunocompromising condition, cerebrospinal fluid leak, or cochlear implant who previously received a 13-valent pneumococcal conjugate vaccine (PCV13) | CDC. September 25, 2023. Accessed August 25, 2024. https://www.cdc.gov/vaccines/acip/recs/grade/PCV20-prev-vax-adults-19-64-risk-based.html
  3. Platt H, Omole T, Cardona J, et al. Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial. The Lancet Infectious diseases. Published online September 15, 2022. doi:10.1016/s1473-3099(22)00526-6
  4. Merck Sharp & Dohme LLC. A Phase 3, Randomized, Double-Blind, Active Comparator-Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-Naïve Adults. clinicaltrials.gov; 2023. Accessed December 31, 2023. https://clinicaltrials.gov/study/NCT05425732
  5. Merck Sharp & Dohme LLC. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-Experienced Adults 50 Years of Age or Older. clinicaltrials.gov; 2024. Accessed December 31, 2023. https://clinicaltrials.gov/study/NCT05420961
  6. Merck Sharp & Dohme LLC. A Phase 3, Multicenter, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Adults Living With HIV. clinicaltrials.gov; 2024. Accessed December 31, 2023. https://clinicaltrials.gov/study/NCT05393037
  7. Merck Sharp & Dohme LLC. A Phase 3 Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 When Administered Concomitantly With Influenza Vaccine in Adults 50 Years of Age or Older. clinicaltrials.gov; 2023. Accessed December 31, 2023. https://clinicaltrials.gov/study/NCT05526716
  8. Merck Sharp & Dohme LLC. A Phase 3 Randomized, Double-Blind, Active Comparator-Controlled, Lot-to-Lot Consistency Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age. clinicaltrials.gov; 2024. Accessed December 31, 2023. https://clinicaltrials.gov/study/NCT05464420