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)








GRADE: PCV15 use in children aged 2–18 years with certain underlying medical conditions that increase the risk of pneumococcal disease										Related Pages
										Introduction
On June 22, 2022, ACIP recommended use of 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) as an option for pneumococcal conjugate vaccination for persons aged <19 years according to currently recommended PCV13 dosing and schedules. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was employed to guide 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 PCV15 among pediatric age groups for which the vaccine was approved. Since only immunogenicity and safety data were available for PCV15, the search included 13-valent pneumococcal conjugate vaccine ((PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.]) efficacy or effectiveness studies to help interpret PCV15 immunogenicity study findings. GRADE assessment was performed for PCV15 studies only. 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).Table 1: Policy Question and PICO
Table 1: Policy Question and PICO
Policy question:
Should PCV15 be recommended as an option for pneumococcal conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged 2 through 18 years of age with underlying medical conditions?Population
U.S. children with underlying medical conditions* 2–18 years of ageIntervention
PCV15 according to dosing and schedules currently recommended for PCV13Comparison
PCV13 according to currently recommended dosing and schedulesOutcomes
Vaccine-type invasive pneumococcal disease, vaccine-type pneumonia, vaccine-type acute otitis media, vaccine-type pneumococcal deaths, serious adverse events following immunization* Underlying medical conditions defined as cerebrospinal fluid leak; chronic renal failure or nephrotic syndrome; cochlear implant; 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; sickle cell disease and other hemoglobinopathies. For children aged 2–5 years, also includes chronic heart or lung disease, diabetes mellitus.This systematic review leveraged strategies used in existing systematic reviews, which captured literature published between January 1994–December 2019 targeting PCV7, PCV10 and PCV13 using various dosing schedules in the general pediatric population. Specifically, we utilized:
Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules (Loo 2014); searched literature from January 1994 – September 2010
Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules and Products (Cohen 2017); searched literature from October 2010 – December 2016
Updated literature search to Cohen 2017, which was conducted to review evidence regarding dosing schedule changes; searched literature from January 2017 – December 2019In addition, we conducted a search of literature published during January 2010 – October 2021 from the following databases: Medline (OVID), Embase (OVID), Cochrane Library, CINAHL (EbscoHost), Scopus (for WOS). The search terms are included in Appendix 1. The updated search sought to capture:
Pneumococcal vaccine studies specifically targeting children with underlying medical conditions, which were not captured in the previous literature searches
Additional literature on pneumococcal vaccines published since January 2020 to update the previous systematic reviews evaluating PCV13 use in the general pediatric populationSearch results were supplemented by an updated Pubmed search using “V114*” or “PCV15” and a search of clinicaltrials.gov using “V114”. Unpublished data were provided by the vaccine manufacturer.
Studies with primary data on PCV15 use in children 2 – 18 years of age with underlying medical conditions were included. Seventy-one studies were initially identified; after screening, deduplication and exclusion, 2 were included for GRADE. Characteristics of these studied are included in Appendix 2.  No PCV15 studies directly assessed vaccine effectiveness against the critical outcomes.  Beneficial and harmful outcomes for the GRADE assessment were selected by the ACIP Pneumococcal Vaccines Work Group during 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 acute otitis media, vaccine-type pneumococcal deaths, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).
*V114 is the name used for Merck’s investigational 15-valent pneumococcal conjugate vaccine candidateTable 2: Outcomes and Rankings
Table 2: Outcomes and Rankings
Outcome
Importance*
Included in evidence profileVaccine-type invasive pneumococcal disease
Critical
No**Vaccine-type pneumonia
Critical
No**Vaccine-type acute otitis media
Critical
No**Vaccine-type pneumococcal deaths
Critical
No**Serious adverse events following immunization
Critical
Yes
*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making
**No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomesTable 3a. Summary of Studies Reporting Immunogenicity
Table 3a. Summary of Studies Reporting Immunogenicity
Author, year
Study design; population and age
N intervention
N comparison
Comparator vaccine
IgG GMC ratios [range (serotype)]*
Absolute difference in % seroresponders (serotype)
Interpretation**
Study limitations (Risk of Bias)V114-023
Merck, unpublished
Phase 3 RCT (one dose of V114 vs. PCV13), children with sickle cell disease, 5 – 17 years
69
34
PCV13
0.54 (4) to 1.67 (6B)
Not reported
**GMC ratio (post-dose 1):**
PCV15 > PCV13 for 6/13 shared st
PCV15 > PCV13 for 22F and 33F
Not seriousV114-030
Merck, unpublished
Phase 3 RCT (V114+PPSV23 vs. PCV13 + PPSV23), children living with HIV, 6 – 17 years
203
204
PCV13 followed by PPSV23 8 weeks later
Post-PCV:
0.61 (4) to 1.65 (6B)
Post-PPSV23:
0.65 (4) to 1.43 (6B)
Not reported
**Post-PCV:**
PCV15 > PCV13 for 8/13 shared st; significant for st3 and 6B
PCV15 = PCV13 for 18C
PCV15 > PCV13 for 22F and 33F**Post-PPSV23:**
PCV15+PPSV23 > PCV13 + PPSV23 for 3/13 shared st; significant for 6B
PCV15+PPSV23 < PCV13 + PPSV23 for 22F and 33F
Not serious
GMC = Geometric mean concentration; st = serotype; RCT = randomized controlled trial; V114 = 15-valent pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine
* IgG GMC ratio = [GMC (PCV15)] / [GMC (comparator vaccine)]
**Blood draws occurred 30 days post-doseTable 3b. Summary of Studies Reporting Safety
Table 3b. Summary of Studies Reporting Safety
Author, year
Study Design; population and age
N intervention
N comparison
Comparator vaccine
Absolute % difference
(% SAE PCV15 –
% SAE comparator)*
N related to vaccine
Study limitations (Risk of Bias)V114-023
Merck, unpublished
Phase 3 RCT, children with sickle cell disease, 5 – 17 years
69
34
PCV13
-4.7
0
Not seriousV114-030
Merck, unpublished
Phase 3 RCT, children living with HIV, 6 – 17 years
203
204
PCV13
0
0
Not serious203
202
PCV13 +
PPSV23
0
0
RCT = randomized controlled trial
*Reported serious adverse events include those that occurred after dose 1 through completion of study participation.Table 4. Grade Summary of Findings Table
Table 4. Grade Summary of Findings Table
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
PCV15
Intervention
PCV13
comparison
Relative
(95% CI)
Absolute
(95% CI)Vaccine effectiveness: Vaccine-type pneumococcal disease (assessed with immunogenicity data)**21,2**
Randomized studies
Not serious
Not serious
Seriousa
Seriousb
Not serious
272
238
Post-PCV dose: PCV15 had higher immune responses (IgG GMC) vs. PCV13 for 6 to 8 PCV13 serotypes and unique serotypes (22F and 33F) across studies.
Post-PPSV23 dose: PCV15 + PPSV23 had higher immune response (IgG GMC) vs. PCV13 + PPSV23 for 3 of 13 PCV13 serotypes, but not for PCV15 unique serotypes (22F and 33F).
3
CriticalSerious adverse events following immunization**21,2**
Randomized studies
Not serious
Not serious
Not serious
Very seriousc
Not serious
0/272
0/238
not estimable
—
3
Critical
These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered
Small sample size
No vaccine-related serious adverse events reported; sample size very small**References**
V114-023. A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (V114-023/PNEU-SICKLE)
V114-030. Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED)Table 5. Summary of Evidence for Outcomes of Interest
Table 5. Summary of Evidence for Outcomes of Interest
Outcome
Importance
Included in profile
CertaintyVT- invasive pneumococcal disease
Critical
No*
3VT- pneumonia
Critical
No*
3Vaccine-type acute otitis media
Critical
No*
3Vaccine-type pneumococcal deaths
Critical
No*
3Serious adverse events following immunization
Critical
Yes
3
*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomesSummary
The evidence type for use of PCV15 in children aged 2–18 years of age with underlying medical conditions was determined to be 3 (low certainty of evidence) for VT-invasive pneumococcal disease, VT-pneumonia, VT-acute otitis media, and VT- pneumococcal deaths and was downgraded once for indirectness due to lack of correlates of protection for the critical outcomes considered and once for imprecision due to small sample sizes of the studies. The evidence type for serious adverse events following immunization was 3 (low certainty of evidence); imprecision was downgraded two points to very serious for few vaccine-related serious adverse events reported and for very small samples sizes of the studies. ACIP reviewed the results of both the GRADE evidence assessment and the Evidence to Recommendations (EtR) framework in February 2022. An updated EtR table was shared with ACIP in June 2022. On June 22, 2022, ACIP recommended use of PCV15 as an option for pneumococcal conjugate vaccination for persons aged <19 years according to currently recommended PCV13 dosing and schedules.
References
Loo JD, Conklin L, Deloria Knoll M, Fleming-Dutra K, et al. Methods for a Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules. PIDJ. 2014; 33(1,S2); S182-S187.
Cohen OG. Pneumococcal Conjugate Vaccine (PCV) Product Assessment. Accessed August 2, 2021 at https://www.jhsph.edu/ivac/wp-content/uploads/2018/05/pcv-product-assessment-april-25-2017.pdf.
Platt HL, Greenberg D, Tapiero B, Clifford RA, Klein NP, Hurley DC. A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants. Pediatric Infectious Diseases Journal 2020.
V114-023. A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (V114-023/PNEU-SICKLE)
V114-030. Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED)Appendices
Appendix 1: Studies Included in the Review of Evidence
Appendix 1. Search strategy
Database
Strategy
Run Date
Records**Medline****(OVID)****1946–**
(((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
Exp Child/ OR (Child* OR pediatric* OR paediatric*).ti,ab,kf,hw.
AND
Trial* OR study OR studies OR rct* OR review.ti,pt.
Limit English; 2010 –
10/20/2021
2864**Embase****(OVID)****1988–**
(((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
Exp Child/ OR (Child* OR pediatric* OR paediatric*).ti,ab,kw,hw.
AND
Trial* OR study OR studies OR rct* OR review.ti,pt.
NOT
exp animal/ NOT exp human/Limit English; 2010 – ; not pubmed/medline ; not conference abstracts
10/20/2021
3236
-2304
duplicates
=932
unique items**Cochrane Library**
[mh “pneumococcal vaccines”] OR (((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”):ti,ab
AND
[mh Child] OR (Child* OR pediatric* OR paediatric*):ti,abLimit English; 2010 –
10/20/2021
331
-192
duplicates
=139
unique items**CINAHL****(EbscoHost)**
(((pneumococcal OR pneumococci OR “streptococcus pneumoni*” OR “s? pneumoni*”) N5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR “pnu immune vaccine*” OR “pnuimmune vaccine*” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
(Child* OR pediatric* OR paediatric*)
Limit English; 2010 – ; exclude Medline records
10/20/2021
345
-267
duplicates
=78
unique items**Scopus**
**TITLE-ABS-KEY**(((pneumococcal OR pneumococci OR “streptococcus pneumoni*” OR “s? pneumoni*”) W/5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR “pnu immune vaccine*” OR “pnuimmune vaccine*” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”) AND**TITLE-ABS-KEY**(Child* OR pediatric* OR paediatric*) AND NOT INDEX(medline)
Limit English; 2010 – ;
10/20/2021
682
-492
duplicates
=190
unique itemsAppendix 2. Studies Included in the Review of Evidence
Appendix 2. Studies Included in the Review of Evidence
Author, year
Study design
Country
Age
Total population
N Intervention
N comparison
Outcomes
Funding sourceV114-023
Merck, unpublished
Phase 3 RCT (one dose of V114 vs. PCV13), children with sickle cell disease, 5 – 17 years
Brazil, Colombia, Dominican Republic, Greece, Italy, Panama, US
5–17 years
103
69
34
Immunogenicity, safety
MerckV114-030
Merck, unpublished
Phase 3 RCT (V114+PPSV23 vs. PCV13 + PPSV23), children living with HIV, 6 – 17 years
South Africa, Thailand, Ukraine
6–17 years
407
203
204
Immunogenicity, safety
Merck
RCT = randomized controlled trial; V114 = 15-valent pneumococcal conjugate vaccineTop of Page
							
					
							Last Reviewed:  August 31, 2022						Source: 	National Center for Immunization and Respiratory Diseases
					Facebook
        Twitter
        LinkedIn
        Syndicate 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