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)








Evidence to Recommendations for PCV15 use among adults ≥65 years old						Print
																Related Pages
					**Question: Should PCV15 in series with PPSV23 vs. Current pneumococcal vaccine recommendation be used in U.S. adults aged ≥65 years for vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumonia, vaccine-type pneumococcal death?**
**Population:**U.S. Adults aged ≥65 years
**Intervention:** PCV15 in series with PPSV23
**Comparison:**Existing pneumococcal vaccine recommendations:
PCV13 followed by PPSV23 (immunocompromised adults* aged ≥65 years)
PPSV23 (immunocompetent adults aged ≥65 years)***immunocompromised adults include adults with immunocompromising condition (chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies), CSF leak, or cochlear implant; immunocompetent adults are those without these conditions.
**PCV13 recommended based on shared clinical decision making for immunocompetent adults ≥65 years
**Outcome:** Vaccine-type invasive pneumococcal disease; Vaccine-type non-bacteremic pneumococcal pneumonia; Vaccine-type pneumococcal death; Serious adverse events following immunization**Background:**
A 15-valent pneumococcal conjugate vaccine (PCV15, Merck) was licensed for use in adults on July 16, 2021. Unlike previous conjugate vaccine formulations, PCV15 was licensed for adults before it was licensed for children.
Until October 20, 2021, two pneumococcal vaccines (13-valent pneumococcal conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]) were recommended for use in adults, and the recommendations varied by age- and risk-groups. The ACIP Pneumococcal Vaccines Work Group reviewed available data to inform the use of PCV15 in adults in order to identify policy options that maximize pneumococcal disease prevention among adults, reduce disparity, and simplify existing recommendations to improve vaccine uptake.Problem
Resource use model, base, range
Criteria
Work Group Judgments
Evidence
Additional InformationIs the problem of public health importance?
Yes
In adults, the burden of pneumococcal disease increases with age. Adults aged ≥65 years comprise 22% of all U.S. adults aged ≥19 years and approximately 40-55% of pneumococcal disease burden is in adults aged ≥65 years.
In 2018, invasive pneumococcal disease (IPD) incidence was approximately 24 per 100,000 population with a case fatality ratio of 14% in adults aged ≥65 years. IPD incidence caused by serotypes contained in the 13-valent pneumococcal conjugate vaccine (PCV13) has been stable since 2014, with serotype 3 as the most common serotype. Among all IPD serotypes in 2018–2019, PCV13 serotypes comprised 27% of IPD and additional serotypes included in PCV15 and PCV20 (but not in PCV13) comprised 15% and 29% of the IPD burden, respectively.
The estimated burden of pneumococcal pneumonia has been variable. According to CDC’s Surveillance for Non-invasive Pneumococcal Pneumonia (SNiPP), incidence of hospitalized pneumococcal pneumonia was approximately 105 per 100,000 population in adults aged ≥65 years in 2017.  Based on a prospective multicenter surveillance study of adults hospitalized with community-acquired pneumonia conducted in 2013–2016, 8% had pneumococcal pneumonia, 4% had PCV13-type pneumonia, 6% were due to PCV15-types, and 7% were due to PCV20-types [1].Benefits and Harms
Benefits and Harms
Criteria
Work Group Judgments
Research Evidence
Additional InformationHow substantial are the desirable anticipated effects?
Moderate
We identified three Phase 3 randomized-controlled trials comparing the immunogenicity of PCV15 in series with PPSV23 to PCV13 in series with PPSV23[2-4] (please refer to GRADE tables for details). These studies did not assess statistical non-inferiority or superiority.
In healthy adults aged ≥50 years [4], geometric mean titer (GMT) was higher in the group that received PCV15 in 13/13 shared PCV13 serotypes and GMT ratios were significantly higher in three (serotypes 1, 14, 23F); % seroresponders (% of subjects with ≥4-fold risk in OPA GMT post-vaccination) was higher in 11/13 shared serotypes (all non-significant).
In Navajo adults or adults with chronic underlying medical conditions aged 18–49 years [2], PCV15 elicited higher GMTs in 9/13 serotypes, and higher % seroresponders in 5/13 serotypes (non-significant).
In adults aged ≥18 years with HIV infection [3], PCV15 elicited higher GMTs in 11/13 serotypes and higher % seroresponders in 10/13 serotype.
In all 3 studies, improved immunologic responses against serotype 3 were observed 30 days after administration of PCV15 compared with PCV13; however, the improved immunologic responses against serotype 3 were diminished when immunologic responses were assessed after administration of PPSV23 [2-4]
Improved immunologic responses against PCV15-unique serotypes 22F and 33F were observed 30 days after administration of PCV15 compared with PCV13; however, the improved immunologic responses against serotypes 22F and 33F were diminished when immunologic responses were assessed after administration of PPSV23 [2-4]
No PCV15 studies directly assessed the impact on critical outcomes.
Although subjects who received PCV15 in series with PPSV23 generally had higher geometric mean titers (GMTs) and % who had ≥4-fold rise in OPA GMT pre-/post-vaccination compared with subjects who received PCV13 in series with PPSV23, the clinical significance remains unknown.
The 2014 recommendation to routinely use PCV13 in series with PPSV23 in adults aged ≥65 years did not significantly impact PCV13-type disease at the population level; as such, routine PCV13 use recommendation in adults without immunocompromising conditions, cochlear implant, or CSF leak was removed in 2019 [5], recognizing that historically low levels of PCV13-type disease in adults aged ≥65 years was primarily attained through indirect effects from pediatric PCV13 use in children. Anticipating pediatric licensure of PCV15, some WG members believed that the incremental benefit of routine PCV15 use in series with PPSV23 in adults aged ≥65 years may be small.
Given that PCV15 provides coverage for 2 additional serotypes (approximately 15% of remaining IPD burden) compared with PCV13, the magnitude of the desirable anticipated effects was estimated to be small to moderate, or higher if the enhanced immune response to ST3 provided clinical protection.**Conclusion:**
Despite uncertainties about the clinical significance of immunogenicity study results, the Work Group believed that the potential benefit from PCV15 in series with PPSV23 use is moderate compared with the existing recommendationsHow substantial are the undesirable anticipated effects?
Minimal
Safety data from phase 3 randomized-controlled trials [2-4] showed that the percentage of subjects with serious adverse events were low; slightly lower in subjects who received PCV15 compared with those who received PCV13 (0.3–1.3% vs. 0.7–4.1%). None of the serious adverse events were associated with the vaccines.Do the desirable effects outweigh the undesirable effects?
Favors intervention
The Work Group decided that the desirable effects of the Merck PCV15 in series with PPSV23 outweigh the undesirable effects.What is the overall certainty of this evidence for the critical outcomes?
Effectiveness of the intervention is Level 2 (moderate)
Safety of the intervention is Level 2 (Moderate)
For the critical outcomes, the certainty of evidence was moderate for both the effectiveness and safety of the intervention.Values
Values
Criteria
Work Group Judgments
Research Evidence
Additional InformationDoes the target population feel that the desirable effects are large relative to undesirable effects?
Probably yes
No data are available on values of the target population toward use of PCV15 in series with PPSV23. All identified studies in adults[6-9] were performed before 2019, and most targeted a specific population with high representation of Blacks or Hispanics. Therefore, the survey sample populations may not be representative, limiting the generalizability to all U.S. adults aged ≥65 years.
The Work Group determined that most adults aged ≥65 years would value the individual level protection from PCV15 vaccination in series with PPSV23 above the potential side effects. The existing pneumococcal vaccine recommendation is similar to the new intervention, and the proportion of adults who received both PCV13 and PPSV23 have increased over time.Is there important uncertainty about or variability in how much people value the main outcomes?
Probably no important uncertainty or variability
No evidence was identified.
The Work Group determined that whereas there might be variability and uncertainty in how populations value the vaccine, for most, the desirable effects probably outweigh the undesirable effects.Acceptability
Acceptability
Criteria
Work Group Judgments
Research Evidence
Additional InformationIs the intervention acceptable to key stakeholders?
Probably yes
Key findings from provider and immunization manager surveys [10-12]:
The recommendation of PCV13 use based on shared clinical decision-making is confusing
Preference for a simplified pneumococcal vaccine recommendation
Responses were mixed about use of PCV in series with PPSV23. In one survey [12], routine PCV use in series with PPSV23 was the most preferred among those provided options on vaccine recommendations, which included use of PCV routinely vs shared clinical decision-making, and with or without PPSV23. In another survey [11], concerns related to implementation (e.g., challenges in determining pneumococcal vaccination history, increased changes of dosing errors), communication, and series completion especially in hard-to-reach population were expressed.
Routine use of PCV13 in series with PPSV23 was implemented in 2014 [13]. Since some adults aged ≥65 years continue to receive PCV13 in series with PPSV23 after the shared clinical decision-making recommendation in 2019, the intervention may be acceptable to some providers.
Work Group members agreed that recommending both PCV15 and PPSV23 to all adults aged ≥65 years will simplify the existing recommendations.Resource Use
Resource Use
Criteria
Work Group Judgments
Research Evidence
Additional InformationIs the intervention a reasonable and efficient allocation of resources?
Probably no
Two cost-effectiveness analysis models were reviewed. These models assessed the economic impact of use of PCV15 in series with PPSV23 in adults aged ≥65 years.
In the CDC model, use of PCV15 in series with PPSV23 for adults at age 65 years was estimated to be cost-saving (i.e., an intervention strategy that yields higher health outcomes and lower costs) compared to the existing recommendation. Cost-savings were found in 4/4 scenarios investigated with the CDC model. In the Merck model, the estimated cost per QALY gained ranged from $237,000 to $282,000 in the base case and found cost-savings in a scenario that utilized alternative vaccine coverage assumptions. In both models, use of PCV15 in series with PPSV23 for adults at age 65 years prevented more disease compared to the existing recommendation.
Differences across models were likely due to differences in model structure and uncertainties about serotype-specific vaccine effectiveness and vaccine coverage following a change in recommendations.
Some key differences between the two models included:
Vaccine coverage assumptions
Serotype specific vaccine effectiveness assumptions
Transitions to higher levels of disease risk for individuals in the model who started at a lower risk statusOther important assumptions included:
Waning immunity
Incidence of pneumonia and IPDEquity
Equity
Criteria
Work Group Judgments
Research Evidence
Additional InformationWhat would be the impact on health equity?
Probably no impact
Disparities in pneumococcal disease burdenIndirect effects from pediatric PCV13 vaccination reduced PCV13-type IPD incidence among those with increased IPD burden including Black [14] and Navajo[15] adults. Among racial groups, most of the remaining disparity in IPD burden was in non-PPSV23-type disease. Despite indirect effects from pediatric PCV13 vaccination, burden of PCV13-type IPD remains higher in Navajo and Alaska Native adults compared with the general adult population. Therefore, use of new vaccines may reduce, but not eliminate, disparities in disease burden.
Disparities in pneumococcal vaccine coverageAn analysis of PCV13 and PPSV23 claims data of Medicare beneficiaries aged ≥65 years showed that in 2013 when routine use of PPSV23 was recommended for all adults aged ≥65 years without immunocompromising conditions, the proportion of beneficiaries who received at least one dose of PPSV23 was highest in Whites (46%) and lowest in Hispanics (33%%) [16]. In 2018 when all adults aged ≥65 years were recommended to receive PCV13 in series with PPSV23, the proportion of adults who received both PCV13 and PPSV23 was the highest in Whites (31%) and the lowest was in Hispanics (14%) [16].
Some Work Group members believed that a recommendation that requires two vaccines is more likely to disadvantage the population who may have increased pneumococcal disease burden and have lower vaccine coverage or challenges with access to care.
Some members thought that routine use of PCV15 in series with PPSV23 for all adults aged ≥65 years simplifies the recommendation and would lead to higher coverage and possibly improving equity.
Overall, the Work Group believed that the new policy option will likely have little impact on equity for adults aged ≥65 years compared with the current recommendation.Feasibility
Feasibility
Criteria
Work Group Judgments
Research Evidence
Additional InformationIs the intervention feasible to implement?
Probably yes
In 2014, PCV13 was recommended in series with PPSV23 for all adults aged ≥65 years [13]. The Work Group believed that routine use of PCV15 in series with PPSV23 will be a simplification of the PCV13 use recommendation based on shared clinical decision-making for adults without immunocompromising conditions, CSF leaks or cochlear implants[5].
Compared with a single-dose vaccine recommendation, a recommendation that requires vaccination with 2 different pneumococcal vaccines is more challenging to implement and is more likely to disadvantage adults with challenges with healthcare access. Providers often have challenges in determining accurate pneumococcal vaccination history to complete the recommended vaccine series.Balance of Consequences
The balance between desirable and undesirable consequences is closely balanced or uncertain.
Additional Considerations
The Work Group interpretation on balance of consequences was initially split between “Undesirable consequences probably outweigh desirable consequences in most settings” and “The balance between desirable and undesirable consequences is closely balanced or uncertain”. While use of PCV15 in series with PPSV23 is likely to prevent pneumococcal disease caused by additional serotypes included in PCV15 but not in PCV13, and there is a potential for improved protection against ST3 disease (the most common remaining PCV13-type disease), some Work Group members believed that the additional benefit may be small based on the 2014–2019  experience from routine PCV13 use in series with PPSV23 for all adults aged ≥65 years[13]. Additionally, some Work Group members believed that there may be potential undesirable consequences in the domains of health equity (a routine recommendation that requires >1 vaccine dose is likely to disadvantage those with healthcare access issues), resource use (based on findings from the initial CDC model), and feasibility (challenges with implementation and access for patients with routine use of PCV15 and PPSV23 series).
Since June, we reviewed updated cost-effectiveness analysis (CEA) results, which included updated model structure (e.g., assessing the impact of age-based recommendation only, vs. assessing the combined impact or risk- and age-based recommendations) and model assumptions (e.g., more rapid waning of PCV, improved VE against vaccine-type IPD for PPSV23 in healthy/CMC adults), and results from other groups. The updated CEA findings showed that use of PCV15 in series with PPSV23 was cost-saving in the CDC model, and prevented more disease in others compared with the existing recommendations.
Based on these updated findings, the WG determined that the balance between desirable and undesirable consequences is closely balanced or uncertain when recommending PCV15 in series with PPSV23 for all adults aged ≥65 years.References
Isturiz R, Grant L, Gray S, Alexander-Parrish R, Jiang Q, Jodar L, et al. Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-Acquired Pneumonia in Hospitalized US Adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021.
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAXTM23 in Adults at Increased Risk for Pneumococcal Disease (V114-017/PNEU-DAY). https://ClinicalTrials.gov/show/NCT03547167.
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAXTM23 in Adults Infected With Human Immunodeficiency Virus (HIV) (V114-018). https://ClinicalTrials.gov/show/NCT03480802.
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAXTM23 in Healthy Adults 50 Years of Age or Older (V114-016/PNEU-PATH). https://ClinicalTrials.gov/show/NCT03480763.
Matanock A, Lee G, Gierke R, Kobayashi M, Leidner A, Pilishvili T. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged >/=65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morbidity and mortality weekly report. 2019;68:1069-75.
Albright K, Hurley LP, Lockhart S, Gurfinkel D, Beaty B, Dickinson LM, et al. Attitudes about adult vaccines and reminder/recall in a safety net population. Vaccine. 2017;35:7292-6.
Lu PJ, O’Halloran A, Kennedy ED, Williams WW, Kim D, Fiebelkorn AP, et al. Awareness among adults of vaccine-preventable diseases and recommended vaccinations, United States, 2015. Vaccine. 2017;35:3104-15.
Brown T, Goldman SN, Acosta F, Garrett AM, Lee JY, Persell SD, et al. Understanding Black Patients’ Refusal of Pneumococcal Vaccination. J Racial Ethn Health Disparities. 2017;4:1-8.
Kaljee LM, Kilgore P, Prentiss T, Lamerato L, Moreno D, Arshad S, et al. “You need to be an advocate for yourself”: Factors associated with decision-making regarding influenza and pneumococcal vaccine use among US older adults from within a large metropolitan health system. Human vaccines & immunotherapeutics. 2017;13:206-12.
Hurley LP, O’Leary ST, Kobayashi M, Crane LA, Cataldi J, Brtnikova M, et al. Physician survey regarding updated PCV13 vaccine recommendations for adults ≥65 years. J Am Geriatr Soc. 2021.
Association of Immunization Managers. 2021 AIM PCV ACIP Survey. 2021.
Myers K, Poulos C, Sweeney C, Vietry J, Snow V, Chilson E. US Health Care Providers’ Preferences for Adult Pneumococcal Vaccine Recommendations. Pfizer, Inc. ; 2021.
Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, et al. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged >/=65 Years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbidity and mortality weekly report. 2014;63:822-5.
Active Bacterial Core Surveillance (ABCs) program. Centers for Disease Control and Prevention; unpublished data, September, 2013.
Johns Hopkins Bloomberg School of Public Health. Center for American Indian Health Unpublished data. 2021.
Hoehner J, Razzaghi H, Williams WW, Kobayashi M, Jatlaoui TC, Wu X, et al. Pneumococcal vaccination among U.S. Medicare beneficiaries aged >=65 years, 2010-2019, Unpublished data.
							
					
							Last Reviewed:  January 27, 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