EtR Framework for Adults Aged 50–64 Years Who Currently Do Not Have a Risk-Based Pneumococcal Vaccine Indication

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Question: Should 21-valent pneumococcal conjugate vaccine (PCV21) be recommended for U.S. adults aged 50–64 years who currently do not have a risk-based pneumococcal vaccine indication?
Population: U.S. adults aged 50–64 years who currently do not have a pneumococcal vaccine indication
Intervention: One dose of PCV21
Comparison: No vaccine
Main outcomes: Vaccine-type invasive pneumococcal disease; Vaccine-type non-bacteremic pneumococcal pneumonia; Vaccine-type pneumococcal death; Serious adverse events following immunization
Setting: Currently, adults aged 19–64 years with a risk condition* are recommended to receive a pneumococcal conjugate vaccine. Expanding the recommendation to adults aged 50–64 years without a risk-based vaccine indication will imply a new age-based recommendation for adults aged ≥50 years.

*Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes mellitus; generalized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome; solid organ transplant; sickle cell disease; or other hemoglobinopathies.
Perspective: Clinical perspective
Background:
  • On June 17, 2024, 21-valent pneumococcal conjugate vaccine (PCV21, Merck) was licensed for use in adults aged ≥18 years.
  • Unlike previous PCVs that were developed to target disease in children, PCV21 was developed to target pneumococcal disease in adults. It does not contain certain serotypes that are included in currently recommended PCVs (e.g., serotypes 1, 4, 5, 6B, 9V 14, 18C, 19F, and 23F in both PCV15 and PCV20; serotype 15B in PCV20) and instead, contains 8 new serotypes that are not included in currently recommended vaccines (e.g., serotypes 15A, 15C, 16F, 23A, 23B, 23F, 31, 35B).
  • The ACIP Pneumococcal Vaccines Work Group reviewed available data to inform the use of PCV21 in adults and identified policy options that maximize pneumococcal disease prevention among adults, reduce disparity, and simplify recommendations to improve vaccine uptake.

Public Health Importance

Problem
Criteria Work Group Judgements Evidence Additional Information
Is the problem of public health importance? Probably yes Prior to the COVID-19 pandemic, it was estimated that ≥100,000 non-invasive pneumococcal pneumonia hospitalizations and ≥30,000 invasive pneumococcal disease (IPD) cases (IPD defined as disease with pneumococcal detection in a normally sterile site) occurred among U.S. adults each year. In 2019, IPD incidence in adults was 4.6, 15.7, and 23.7 per 100,000 population in those aged 19–49 years, 50–64 years, and ≥65 years, respectively1, with rates in adults aged 50–64 years exceeding those in children aged <5 years. In 2020, IPD rates decreased in all age groups, likely due to COVID-19 non-pharmaceutical interventions that resulted in cessation of transmission of non-SARS-CoV-2 respiratory pathogens2. However, relaxation of COVID-19-related interventions resulted in an increase in transmission of these pathogens in more recent years3,4. Data from 2022 show that IPD rates have been nearing pre-COVID-19 baseline. Based on serotype distribution of IDP cases reported in 2018–2022, PCV20 and PCV21 covered 54% and 84% of IPD cases, respectively, in adults aged ≥65 years. In adults aged 50–64 years, the proportions were 56% and 83%, respectively.
Ascertainment of the true burden of non-bacteremic pneumococcal pneumonia is more challenging since the cause of pneumonia is not routinely tested or identified. An analysis using claims data from 2016–2019 reported that the incidence rates of all-cause pneumonia in any setting increase by age at 953, 2679, and 6930 per 100,000 person-years in adults aged 18–49 years, 50–64 years, and ≥65 years, respectively5.
A study conducted among adults aged ≥18 years hospitalized with community-acquired pneumonia (CAP) in Georgia and Tennessee (PNEUMO study) estimated the proportion of vaccine-type pneumococcal pneumonia among CAP cases using their serotype-specific urinary antigen detection (SSUAD) assays for 30 serotypes contained in PCV15, PCV20, and PCV21 except for serotype 15B (included in PCV20). Results showed that among all adults, 12.1% had pneumococcal detection, 9.3% had a pneumococcal serotype contained in PCV21, and 4.1% with a serotype unique to PCV21 (not contained in PCV15 or PCV20)6. By age group, the proportion of PCV21, PCV20 (without serotype 15B), and PCV15 serotypes were: 8.0%, 4.7%, and 4.0% (18–49 years); 11.3%, 8.4%, and 7.3% (50–64 years old); and 8.7%, 6.9%, and 5.8% (≥65 years).
  • Disease incidence in adults aged 50–64 years overall is lower compared with adults aged ≥65 years

Benefits and Harms

Benefits and Harms
Criteria Work Group Judgements Evidence Additional Information
How substantial are the desirable anticipated effects? Small

Moderate

 Findings from one Phase II7 and two Phase III clinical trials8,9 randomized controlled trials (RCT) compared the immunogenicity of PCV21 to that of comparator vaccines (23-valent pneumococcal polysaccharide vaccine [PPSV23], PCV20, PCV15). One study assessed the safety and immunogenicity of V116 with concomitant or sequential administration of the quadrivalent influenza vaccine10.
In the Phase II clinical trial conducted among non-immunocompromised pneumococcal vaccine-naive U.S. adults aged ≥50 years with or without stable chronic medical conditions7, PCV21 met non-inferiority criteria for 9/9 shared serotypes (defined as the lower bound of the 95% confidence interval [CI] of the estimated OPA GMT ratio [PCV21/PPSV23] to be >0.33) and superiority criteria (lower bound of the 95% CI of the estimated GMT ratio to be >1.0) for 12/12 serotypes unique to PCV21 (unique serotypes) when compared with PPSV23.
In the pivotal Phase III clinical trial conducted among non-immunocompromised, pneumococcal vaccine naive adults aged ≥18 years9, those who received PCV21 had a numerically higher OPA GMT for 6/10 shared serotypes compared with those who received PCV20; for 4/6, the 95% CI of the OPA GMT ratios (PCV21/PPSV23) did not cross 1. PCV21 met non-inferiority criteria (defined as the lower bound of the 2-sided 95% CI of the OPA GMT ratio [PCV21/PCV20] to be >0.5) for 10/10 shared serotypes. For the serotypes unique to PCV21, both OPA GMT and % seroresponders were higher among those who received PCV21 compared with PCV20; PCV21 met superiority criteria for 10/11 unique serotypes (not serotype 15C) for both endpoints (GMT ratio: defined as lower bound of the 2-sided 95% CI of the OPA GMT ratio [PCV21/PCV20] to be >2.0; difference in proportions of participants with ≥4-fold rise in serotype-specific OPA responses from baseline to 30 days: lower bound of the 2-sided 95% CI of the differences [PCV21/PCV20] between the proportion of participants with ≥4-fold rise from baseline to 30 days postvaccination to be >0.1).
In a Phase III clinical trial among non-immunocompromised adults aged ≥50 years who previously received a pneumococcal vaccine (PCV13 or PPSV23) ≥1 year prior to enrollment, receipt of PCV21 was compared with a comparator vaccine (PCV15 if previously received PPSV23; PPSV23 if previously received PCV13). In addition, adults who previously received both PCV13 and PPSV23 ≥1 year prior received PCV21 without a comparator group8. Among PPSV23-vaccinated adults, OPA GMT was numerically higher in 4/6 shared serotypes and for 15/15 unique serotypes among PCV21 vs PCV15 recipients. % seroresponders were numerically higher for 1/6 shared serotypes and for 15/15 unique serotypes among PCV21 vs PCV15 recipients. Among PCV13-vaccinated adults, OPA GMT was numerically higher in 7/12 shared serotypes and for 9/9 unique serotypes among PCV21 vs PPSV23 recipients. % seroresponders were numerically higher for 6/12 shared serotypes and for 9/9 unique serotypes among PCV21 vs PPSV23 recipients.
In a Phase III clinical trial among adults aged ≥18 years living with HIV11 (36% of the participants had previously received PCV13 or PPSV23), OPA GMT was numerically higher for 7/13 shared serotypes among PCV21 recipients (PCV21 followed by placebo 8 weeks later) compared with PCV15+PPSV23 recipients (PCV15 followed by PPSV23 8 weeks later) and was higher for 8/8 unique serotypes. % seroresponders was numerically higher for 8/13 shared serotypes and for 8/8 unique serotypes among PCV21 recipients.
Lastly, in a Phase III study among non-immunocompromised adults aged ≥50 years10 (29% previously received PCV13 or PPSV23) who received PCV21 and quadrivalent influenza vaccine (QIV) concomitantly or sequentially (30 days after PCV21 administration), GMT ratio (concomitant group/sequential group) was <1 for all 21 serotypes among those who received PCV21 and QIV sequentially vs. concomitantly; non-inferiority criteria (lower bound of the 95% CI for the estimated GMT ratio >0.5) were met for 20/21 serotypes (not met for serotype 23B).
 There are no studies that have assessed the efficacy or effectiveness of PCV21 against clinical outcomes.
Work Group members in favor of lowering the age-based recommendation to age ≥50 years believed that a more robust immune response could be expected by administering PCV21 at age 50–64 years compared with age ≥65 years and before a portion of that population develops an immunocompromising condition.
On the other hand, some Work Group members expressed concerns that we could miss the opportunity to provide protection against disease later in life when the disease incidence becomes higher if we lowered the age-based recommendation since there are limited data on duration of protection or protection against disease from multiple PCV doses in adults.
How substantial are the undesirable anticipated effects? Minimal PCV21 Clinical Trial Safety Data
Safety data from participants in four PCV21 Phase III clinical trials, i.e., pneumococcal vaccine-naive adults aged 18–49 years9,12, pneumococcal vaccine naive adults aged ≥50 years9,10, and pneumococcal vaccine-experienced adults aged ≥50 years8,10, were pooled. Safety of PCV21 among 4,020 recipients was compared with that among 2,018 recipients of the comparator vaccine (PCV15, PCV20, or PPSV23). The proportion of participants who experienced at least one solicited adverse event was comparable among PCV21 (63.3%) and comparator vaccine (63.9%) recipients. Injection site pain was the most common solicited injection site event (55.6% among all PCV21 versus 54.5% among control vaccine recipients). Among solicited systemic adverse events, the following were more common among all PCV21 recipients than among comparator vaccine recipients: fatigue (27.1% versus 23.7%), headache (18.4% versus 15.5%), and myalgia (11.3% versus 7.5%). Most solicited adverse events were mild (Grade 1) or moderate (Grade 2). A total of four (0.1%) potentially life-threatening (Grade 4) solicited adverse events were reported (three in PCV21 group, one in the control group). All were fever, which resolved. No occurrences of Guillain-Barré syndrome (GBS) were observed.
Across one Phase II clinical trial 7 and five Phase III clinical trials9,8,11,10,12, serious adverse events were observed in 74 of 4,963 (1.5%) PCV21 recipients and 49 of 2,472 (2.0%) comparator vaccine recipients through six months postvaccination*. Two serious adverse events, bronchospasm10 and injection site cellulitis8, were deemed to be vaccine-related in the PCV21 recipients; both resolved.
Post-licensure PCV20 Safety Data
Analysis of reports to the Vaccine Adverse Event Reporting System (VAERS) showed that among 1,976 reports received after PCV20 vaccine in adults aged ≥19 years between October 2021 and December 2023, most reports were classified as non-serious and describe reactions consistent with pre-licensure PCV20 trials in adults13. There was a data mining alert for GBS after PCV20 vaccination. An analysis of Centers for Medicare & Medicaid Services data through November 2023 showed that GBS incidence rate post-PCV20 administration has been rare and that the estimated incidence rate ratios and confidence intervals did not identify statistically significant risk elevation for any of the pre-specified outcomes14.
Do desirable effects outweigh undesirable effects? Favors Intervention
  • Based on available data, the Work Group believed that there are no concerns about the risks outweighing the benefits of PCV21 vaccination.
  • Some Work Group members believed that by lowering the age-based recommendation, we could expect a more robust immune response compared to administering the vaccine later in life. Also, they believed that lowering the age-based recommendation would improve the opportunity to vaccinate adults before they develop an immunocompromising condition.
What is the overall certainty of the evidence of effects? Effectiveness of the intervention

Moderate

Safety of the intervention

Moderate

 GRADE analyses were completed to assess the certainty of evidence.
  • Overall evidence type was moderate for the effectiveness of the intervention.
    • Assessment on indirectness was downgraded to “serious” since only immunogenicity studies were available and there are no established correlates of protection for PCV21 against some of the critical outcomes (vaccine-type non-invasive non-bacteremic pneumococcal pneumonia, vaccine-type pneumococcal disease mortality)
  • Overall evidence type was moderate for the safety of the intervention.
    • Assessment on imprecision was downgraded to “serious” because few vaccine-related serious adverse events were reported in studies with small sample sizes.
 Refer to GRADE summary tables for details. This population is covered in GRADE tables for adults aged 50–64 years who currently do not have a risk-based pneumococcal vaccine indication.

* PCV21 recipient group includes participants who received PCV21 and concomitant influenza vaccine, and participants who received influenza vaccine followed by PCV21

Values

Values
Criteria Work Group Judgements Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? Probably yes

Don't know (minority opinion)

 Evidence to support this discussion for this EtR domain was limited (see summary of surveys conducted among targeted adult population by the Healthcare and Public Perceptions of Immunizations [HaPPI] Survey Collaborative and by Merck in “Additional Considerations” column). The Work Group members found it difficult to understand how the target population would perceive the benefits vs. harms of PCV21. Therefore, some Work Group members selected “Don’t Know” as their interpretation of this EtR domain.
  • An online survey targeting adults aged 19–64 years with underlying conditions with risk-based pneumococcal vaccine indications was conducted by the HaPPI Survey Collaborative in January 202415. Results showed that a higher proportion of participants who self-reported having received a pneumococcal vaccine vs. those who did not had heard of pneumococcal disease and believed they would get pneumococcal disease in the next year. Among those who reported not receiving the pneumococcal vaccine, the most common reasons selected were not knowing they needed to get a pneumococcal vaccine or not being recommended by a healthcare provider that they needed a vaccine. Regardless of self-reported vaccination status, >60% of participants stated that they would receive a pneumococcal vaccine if recommended by a healthcare provider (range: 64% among unvaccinated to 88% among vaccinated).
  • An online survey targeting healthcare consumers (HCC) was conducted by Merck in February 2024. The survey targeted adults aged ≥65 years who previously received a pneumococcal vaccine as an adult or vaccine-naive adults aged 50–64 years without immunocompromising conditions who were neutral or in favor of adult vaccinations.
    • 73% of the of the survey respondents aged 50–64 years showed a positive reaction (i.e., somewhat positive, very positive, and extremely positive combined) to a hypothetical vaccine that had the profiles of PCV21.
Is there important uncertainty about or variability in how much people value the main outcomes? Possibly important uncertainty or variability There was no evidence identified to support the discussion of this question. Some Work Group members believed that patients are likely to follow what the providers recommend.

Acceptability

Acceptability
Criteria Work Group Judgements Evidence Additional Information
Is the intervention acceptable to key stakeholders? Probably yes A Merck-supported cross-sectional online survey was conducted among healthcare providers (HCPs, internal medicine physicians, family medicine physicians, nurse practitioners, physician assistances, pharmacists) in March to May 202416. Participants were predominantly of White race (85.3%) and practiced in an urban location (82.9%). The most important vaccine attributes driving HCP decisions were related to disease coverage. The majority (95.9%) of survey respondents either strongly agreed or agreed to have more approved pneumococcal vaccine options for adults. Most surveyed HCPs were likely to support (90.3%: 32.4% slightly likely, 38.8% likely, 19.1% extremely likely) and implement (91.5%: 31.2% slightly likely, 38.5% likely, 21.8% extremely likely) the recommendation to lower the age-based recommendation from age ≤65 years to age ≤50 years if the ACIP recommendations were to change. Some Work Group members believed that if the age-based recommendation is lowered for PCV21 but not for other vaccines, it could have a different interpretation for acceptability.

Resource Use

Resource Use
Criteria Work Group Judgements Evidence Additional Information
Is the intervention a reasonable and efficient allocation of resources? Probably yes

Yes

 “Probably yes” and “yes” combined were selected by the majority of Work Group members. However, a few members selected “probably no”.
Three economic models (Tulane-CDC, Merck, and Pittsburgh models) assessed the cost-effectiveness of the use of PCV21 among adults who are aged 50-64 but are not currently recommended for PCV. For each of the models, the primary health outcome that was used to assess cost-effectiveness was the quality-adjusted life-year (QALY). Across the three models, base case estimates of the value of using PCV20 and PCV21 in the age range of 50 to 64 ranged from being $3,000 to $630,000 per QALY gained17. Estimated costs varied across vaccines and across models. In the Tulane-CDC model the use of PCV21 at age 50 was compared to risk-based use of PCV21 between ages 50 and 64 and age-based use of PCV21 at age 65. This base case estimate was $270,000 per QALY gained, with a range from $200,000 to $700,000 per QALY gained18. The Merck model assessed PCV21 use at age 50 and 65 vs PCV21 use at age 65 among general risk (i.e., not with chronic medical condition [CMC] or immunocompromising condition [IC]) populations and PCV20 use among CMC/IC populations. The estimates from the Merck model ranged from $110,000 to $260,000 per QALY gained, where the higher value comes from a scenario with indirect effects and without productivity loss from disease-induced death; and the lower value comes from a scenario without indirect effects and with productivity loss from disease-induced death. In the Pittsburgh model, the assessment of PCV21 at ages 50 and 65 was compared to PCV21 at risk-based use from 50-64 and age-based use at age 65. In this comparison, the Pittsburgh model found cost-effectiveness estimates that ranged from $2,700 per QALY gained in the societal perspective to $110,000 per QALY gained in the health sector perspective. For PCV20 in the Pittsburgh model, the assessment of PCV20 at ages 50 and 65 was compared to PCV20 at risk-based use from 50-64 and age-based use at age 65. In this comparison, the Pittsburgh model found cost-effectiveness estimates that ranged from $37,000 per QALY gained in the societal perspective to $150,000 per QALY gained in the health sector perspective17.
 Several key assumptions varied across the three models that were reviewed, including indirect effects from PCV20 use among pediatric populations, the modeling of sequalae following acute pneumococcal disease states, the case-fatality-rates following inpatient non-bacteremic pneumonia, and productivity loss assumptions17. The cost per dose of PCV21 varied across models from $287 in the Merck model, to $319 in the Tulane-CDC model, and to $333 in the Pittsburgh model. These variations in inputs and assumptions contributed to variations observed across the main results estimated by the models. Several limitations applied to all models, including limited available data on vaccine efficacy and duration of protection, the magnitude of indirect effects from PCV use, and the future epidemiology of pneumococcal serotypes that are not included in PCV21 (e.g., serotype 4, 19F).

Equity

Equity
Criteria Work Group Judgements Evidence Additional Information
What would be the impact on health equity? Probably increased Pneumococcal vaccine coverage
Adults aged 19–64 years with risk-based vaccine indication have had lower pneumococcal vaccine coverage compared with adults aged ≥65 years19. Among adults with risk-based indications, differences in vaccine coverage by underlying condition (highest among people living with HIV) and age (higher among older adults) have been reported20. Among those eligible to receive pneumococcal vaccines, racial disparities in pneumococcal vaccination coverage exist, with White adults having higher vaccine coverage compared with other race/ethnicity, especially among adults aged ≥65 years.
Vaccine coverage for vaccines with age-based recommendation
Coverage of ≥1 dose of updated 2023–2024 COVID-19 vaccine was 14.3%, 25.2%, and 40.6% for adults aged 18–49 years, 50–64 years, and ≥65 years, respectively21. 2022–2023 influenza season vaccine coverage was 35.8%, 50.3%, and 68.4% for adults aged 18–49 years, 50–64 years, and ≥65 years, respectively22.
Racial disparities in pneumococcal disease incidence
Racial disparities in pneumococcal disease incidence have existed, with disproportionately higher disease burden among Black adults compared with non-Black adults, resulting in high U.S. societal costs.23–25 Introduction of PCV13 among U.S. children reduced disparities that existed in PCV13-type IPD incidence, likely due to indirect effects from PCV13 vaccination in children, and remaining disparities are primarily due to non-PCV13 serotypes.26
According to CDC’s Active Bacterial Core surveillance data from 2018–2019, IPD rates in Black adults appeared to peak at a younger age (i.e., aged 55–59 years) compared with non-Black adults whose IPD rates increased with increasing age. While these disparities may be driven by multiple factors, higher prevalence of conditions that increase the risk of pneumococcal disease in Black vs non-Black adults aged <65 years may be one contributing factor.23
Racial disparities in the proportion of vaccine serotype coverage
The remaining disparities are driven by non-PCV13 type disease26. Based on 2014–2019 ABCs data, PCV20-non-PCV13 serotypes caused 46% of non-PCV13 IPD cases in adults aged 19–49 years (range: 39% in Black adults to 59% in Asian adults), 43% in adults aged 50–64 years (range: 37% in Black adults to 55% in American Indian/Alaska native [AI/AN] adults), and 38% in adults aged ≥65 years (range: 32% in Black adults to 49% in AI/AN adults). PCV21-non-PCV13 serotypes caused 89% of non-PCV13 IPD cases in adults aged 19–49 years (range: 68% in Asian adults to 94% in AI/AN adults), 90% in adults aged 50–64 years (range: 85% in Asian adults to 91% in White adults), and 86% in adults aged ≥65 years (range: 78% in Asian adults to 90% in AI/AN adults).
Emergence of serotype 4 disease in certain U.S. subpopulations
Increase in IPD caused by pneumococcal serotype 4 has been reported in recent years among certain subpopulations, such as in Western United States (especially people experiencing homelessness)27, adults in Alaska28, and adults in the Navajo Nation29. Serotype 4 is included in PCV7 and other licensed pneumococcal vaccines but not in PCV21 and had nearly been eliminated after PCV7 introduction in children. Affected adults are typically adults aged <65 years with underlying conditions with risk-based vaccine indications or with history of substance abuse.
 Some Work Group members expressed the potential for unintended consequences of worsening healthy equity by improving access to vaccines who already have good access to care and not reaching those in need.

Feasibility

Feasibility
Criteria Work Group Judgements Evidence Additional Information
Is the intervention feasible to implement? Probably yes

Yes

 Since recommending PCV21 for adults aged 50–64 years who currently do not have a pneumococcal vaccine indication implies a new age-based recommendation for aged ≥50 years, the Work Group members believed that the recommendation was feasible to implement. Some Work Group members expressed that feasibility may also depend on whether there are different age-based recommendations for PCV21 and other PCVs (e.g., PCV15, PCV20).

Balance of Consequences:

Desirable consequences probably outweigh undesirable consequences in most settings

Additional considerations (optional)

The Work Group could not reach a consensus regarding whether PCV21 should be recommended for adults aged 50–64 years who currently do not have a pneumococcal vaccine indication. The majority of the Work Group members believed that the age-based recommendation should be lowered for other PCVs (e.g., PCV15, PCV20). At the June ACIP meeting, a summary of Work Group deliberations was shared for feedback from the Committee.

While “Desirable consequences probably outweigh undesirable consequences in most settings” was most frequently selected, this was not selected by the majority of Work Group members. Some selected “Desirable consequences clearly outweigh undesirable consequences“ and “The balance between desirable and undesirable consequences is closely balanced or uncertain”, but few believed that undesirable consequences outweighed desirable consequences. The Work Group members acknowledged the potential of preventing more disease and improving health equity by lowering the age-based recommendation for PCV21 from the current ≥65 years to ≥50 years, since lowering the age-based recommendation is expected to improve vaccine coverage for adults who currently have indications for risk-based vaccine recommendations. On the other hand, some Work Group members expressed uncertainties regarding duration of protection from vaccination, the potential for worsening health equity by improving access to those who already have good access to healthcare, and serotype 4 disease trends. Some also expressed concerns regarding the unfavorable findings from some economic models, and the potential implementation challenges of having different PCV recommendations by product (1 PCV option for adults aged 50–64 years without a risk condition, and 3 PCV options for adults with a risk condition).

Additional ACIP considerations

Some Committee members were in favor of lowering the age-based recommendation given the opportunity to improve health equity (especially given the high IPD rates in Black adults compared with non-Black adults in those aged 50–64 years), ease of implementing the recommendation compared with a risk-based vaccine recommendation, the opportunity to vaccinate adults at a younger age before developing immune senescence, and given that 30–50% of adults in this age group already have a risk-based pneumococcal vaccine indication. On the other hand, some Committee members expressed concerns about provider confusion and implementation challenges if recommendations were different for PCV21 compared with other PCVs, potential collateral damage on other vaccines given that there are already multiple vaccines recommended for adults, and need for financial stewardship. There are also uncertainties with duration of protection from PCV use in adults. Given these considerations, the Committee requested that the Work Group review evidence on lowering the age-based recommendation for all PCVs (not only for PCV21) to age ≥50 years for discussion at the October 2024 ACIP meeting.

References

  1. Gierke R. Current epidemiology of invasive pneumococcal disease and pneumococcal vaccine coverage in adults. ACIP Presentation Slides: February 28-29, 2024 Meeting. Accessed May 8, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/02-Pneumococcal-Gierke-508.pdf
  2. Prasad N, Rhodes J, Deng L, et al. Changes in the Incidence of Invasive Bacterial Disease During the COVID-19 Pandemic in the United States, 2014-2020. J Infect Dis. 2023;227(7):907-916. doi:10.1093/infdis/jiad028
  3. Accorsi EK, Hall M, Hersh AL, Shah SS, Schrag SJ, Cohen AL. Notes from the Field: Update on Pediatric Intracranial Infections – 19 States and the District of Columbia, January 2016-March 2023. MMWR Morbidity and mortality weekly report. 2023;72(22):608-610. doi:10.15585/mmwr.mm7222a5
  4. Barnes M, Youngkin E, Zipprich J, et al. Notes from the Field: Increase in Pediatric Invasive Group A Streptococcus Infections – Colorado and Minnesota, October-December 2022. MMWR Morbidity and mortality weekly report. 2023;72(10):265-267. doi:10.15585/mmwr.mm7210a4
  5. Grant LR, Meche A, McGrath L, et al. Risk of Pneumococcal Disease in US Adults by Age and Risk Profile. Open Forum Infect Dis. 2023;10(5):ofad192. doi:10.1093/ofid/ofad192
  6. Self W. Interm Results from the PNEUMO Study. ACIP Presentation Slides: February 28-29, 2024 Meeting. Accessed May 16, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/03-Pneumococcal-Self-508.pdf
  7. 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
  8. 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
  9. Platt HL, Bruno C, Buntinx E, et al. Safety, tolerability, and immunogenicity of an adult pneumococcal conjugate vaccine, V116 (STRIDE-3): a randomised, double-blind, active comparator controlled, international phase 3 trial. The Lancet Infectious Diseases. 2024;0(0). doi:10.1016/S1473-3099(24)00344-X
  10. 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
  11. 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
  12. 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
  13. Moro P. Post-licensure safety surveillance of 20-valent pneumococcal conjugate vaccine (PCV20) among U.S. adults in the Vaccine Adverse Event Reporting System (VAERS). ACIP Presentation Slides: February 28-29, 2024 Meeting. Published February 29, 2024. Accessed February 28, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/05-Pneumococcal-Moro-508.pdf
  14. Forshee R. FDA CBER: Safety Assessment of 20-valent Pneumococcal Conjugate Vaccine (PCV20). ACIP Presentation Slides: February 28-29, 2024 Meeting. Published February 29, 2024. Accessed May 24, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/05-Pneumococcal-Forshee-508.pdf
  15. Healthcare and Public Perceptions of Immunizations Survey Collaborative,. Pneumococcal Vaccination Behavior, Knowledge, and Attitudes Among U.S. Adults Aged 19-64 at Increased Risk from Pneumococcal Disease.; 2024.
  16. OPEN Health. Preferences and Attitudes of Healthcare Providers (HCPs) and Adult Healthcare Consumers (HCCs) Towards Pneumococcal Vaccines in the United States (US).; 2024.
  17. Leidner AJ. Summary of three economic analyses on the use of 21-valent pneumococcal conjugate vaccine (PCV21) among adults in the United States. ACIP Presentation Slides: June 26-28, 2024 Meeting. Published June 27, 2024. Accessed June 29, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-06-26-28/03-Pneumococcal-Leidner-508.pdf
  18. Stoecker C. Economic Assessment of PCV21 in U.S. Adults. ACIP Presentation Slides: June 26-28, 2024 Meeting. Published June 27, 2024. Accessed June 29, 2024. https://www.cdc.gov/vaccines/acip/meetings/slides-2024-06-26-28.html
  19. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC. Published September 25, 2023. Accessed May 28, 2024. https://www.cdc.gov/vaccines/imz-managers/coverage/adultvaxview/pubs-resources/vaccination-coverage-adults-2021.html
  20. Ostropolets A, Shoener Dunham L, Johnson KD, Liu J. Pneumococcal vaccination coverage among adults newly diagnosed with underlying medical conditions and regional variation in the U.S. Vaccine. Published online July 5, 2022. doi:10.1016/j.vaccine.2022.06.068
  21. Adult Coverage and Intent | CDC. Published April 9, 2024. Accessed June 3, 2024. https://www.cdc.gov/vaccines/imz-managers/coverage/covidvaxview/interactive/adult-coverage-vaccination.html
  22. Influenza Vaccination Coverage, Adults. Published April 11, 2024. Accessed June 3, 2024. https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-adult-coverage.html
  23. Nowalk MP, Wateska AR, Lin CJ, et al. Racial Disparities in Adult Pneumococcal Vaccination Indications and Pneumococcal Hospitalizations in the U.S. Journal of the National Medical Association. 2019;111(5):540-545. doi:10.1016/j.jnma.2019.04.011
  24. Kobayashi M. October 19, 2022 ACIP Meeting Presentation. Evidence to Recommendations Framework: PCV20 Use among Adults who Previously Received PCV13.
  25. Altawalbeh SM, Wateska AR, Nowalk MP, et al. Societal Cost of Racial Pneumococcal Disease Disparities in US Adults Aged 50 Years or Older. Appl Health Econ Health Policy. 2024;22(1):61-71. doi:10.1007/s40258-023-00854-0
  26. Accorsi EK, Gierke R, Farley MM, et al. Impact of Pneumococcal Conjugate Vaccines on Racial Differences in Invasive Pneumococcal Disease in Black and White Persons in the U.S. from 2008 to 2019. Presented at: 12th International Symposium on Pneumococci & Pneumococcal Disease; 2022; Toronto, Canada.
  27. Beall B, Walker H, Tran T, et al. Upsurge of conjugate vaccine serotype 4 invasive pneumococcal disease clusters among adults experiencing homelessness in California, Colorado, and New Mexico. The Journal of infectious diseases. Published online August 15, 2020. doi:10.1093/infdis/jiaa501
  28. Steinberg J, Bressler SS, Orell L, et al. Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experiencing Homelessness-Alaska, 2011-2020. Clin Infect Dis. 2024;78(1):172-178. doi:10.1093/cid/ciad597
  29. Navajo Epidemiology Center. Serotype 4 Invasive Pneumococcal Disease (IPD) Information for Providers. Published March 2024. Accessed May 28, 2024. https://nec.navajo-nsn.gov/Portals/0/Reports/ST4%20alert%20for%20NN%20providers_2024.0312.pdf
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