Pneumococcal vaccination in adults

INTRODUCTION — 

Pneumococcal vaccination is an important preventive health care measure that substantially reduces the burden of pneumococcal disease in vaccinated individuals and in the population. Pneumococcal vaccination is indicated for adults with risk factors for pneumococcal disease or for severe adverse outcomes should disease occur. Pneumococcal vaccination is also a routine part of infant and childhood immunization schedules worldwide.

This topic will review types of pneumococcal vaccines, indications and approach to vaccine selection, safety of vaccination, and rationale for vaccination.

Pneumococcal vaccination in children is discussed separately. (See "Pneumococcal vaccination in children".)

VACCINE TYPES — 

Two types of pneumococcal vaccines are available for clinical use: pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) (table 1). The active components of both kinds of vaccine are capsular polysaccharides from pneumococcal serotypes that commonly cause invasive disease. (See "Streptococcus pneumoniae: Microbiology and pathogenesis of infection", section on 'Capsule'.)

Polysaccharide vaccines — PPSV is composed of partially purified pneumococcal capsular polysaccharides. The only available formulation contains 23 pneumococcal polysaccharides (PPSV23; Pneumovax or Pnu-Immune) from the 23 serotypes that were the most common cause of pneumococcal disease in adults in the 1980s (table 2). PPSV23 has evolved from being the only available vaccine, to being part of a two-vaccine series along with PCV, to now largely becoming replaced by the higher valent conjugate vaccines (eg, PCV21). However, it remains uncertain whether a conjugate vaccine is truly more effective than PPSV in adults [1].

Conjugate vaccines — Pneumococcal conjugate vaccines (PCV) consist of pneumococcal capsular polysaccharides covalently linked (conjugated) to a protein. Because these were first developed for pediatric use, earlier formulations included serotypes that caused the most disease in children. More recent formulations have included serotypes that commonly cause disease in adults.

Available PCV formulations include the 13-valent PCV (PCV13; Prevnar 13), the 15-valent PCV (PCV15; Vaxneuvance), the 20-valent PCV (PCV20; Prevnar 20), and the 21-valent PCV (PCV21; Capvaxive) with the numbers indicating the number of pneumococcal capsule types included in the vaccine (table 2).

PCV21 was developed specifically for adults and includes serotypes that are more likely to infect adults (table 2) [2-4]; 77 to 85 percent of invasive pneumococcal infections in adults are due to serotypes in PCV21, compared to 54 to 62 percent in PCV20 and 60 to 67 percent in PPSV23 [4]. PCV21 includes only 4 of the 13 serotypes present in PCV13, excluding those that have largely been eliminated from the population thanks to widespread vaccination of infants and children [3]. Prior PCV formulations focused on serotypes causing majority of IPD in children and are approved for both children and adults.

In contrast to PPSV, PCV stimulates mucosal immunity, thereby preventing nasal colonization of Streptococcus pneumoniae. Mucosal immunity leads to two population-level effects: (1) indirect (herd) immunity and (2) emergence of replacement strains. With widespread use of PCV in infants and children, pneumococcal carriage and, therefore, pneumococcal transmission of those PCV vaccine serotypes decreases thus extending protection to unvaccinated individuals of all ages (figure 1). As a result, with the exception of serotypes against which the vaccines are not effective, serotypes present in PCV13 have nearly disappeared from the pediatric and adult populations (table 2). However, as these serotypes disappear, new pneumococcal serotypes emerge to occupy the vacant ecologic niche; these are called "replacement strains." These concepts are discussed in further detail elsewhere in the topic. (See 'Role of indirect effect (herd immunity)' below and 'Role of replacement strains' below.)

APPROACH TO VACCINATION — 

The United States Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) updated its recommendation in 2022 and 2024 [3,5]. The approach of the authors of this topic is largely consistent with the ACIP although varies for certain patient populations. These recommendations are discussed in the sections that follow.

Indications for vaccination — The goal of vaccination in adults is to prevent invasive pneumococcal disease (IPD; eg, bacteremic pneumonia, meningitis) and nonbacteremic pneumococcal pneumonia. In agreement with the ACIP [5,6], we recommend pneumococcal vaccination for (table 3):

●All adults ≥65 years of age. We also suggest vaccination for all adults aged 50 to 64 years of age.

●Adults aged 19 to 49 years with:

•Predisposing chronic medical conditions (eg, chronic lung disease, chronic liver disease, heart failure, diabetes mellitus)

•Increased risk of meningitis (eg, cochlear implant, cerebrospinal fluid [CSF] leak)

•Immunocompromising conditions (eg, human immunodeficiency virus [HIV] infection, hematologic malignancies) and other conditions associated with altered immunocompetence (chronic renal disease, nephrotic syndrome)

•Functional or anatomic asplenia

In addition to the indications outlined by the ACIP, we also recommend pneumococcal vaccination for those with prior history of IPD.

In situations where it is unclear whether pneumococcal vaccination is indicated or not, we choose to vaccinate because the benefits of the vaccine outweigh the minimal risks.

These populations are at increased risk of developing IPD and/or are at higher risk of morbidity and mortality from IPD (figure 2) [7]. While there is evidence that many patients with immunocompromising conditions such as lymphoma or multiple myeloma may not develop antibody following pneumococcal vaccination, the potential benefits of even suboptimal responses greatly outweigh the risks and the cost is regarded as appropriate for the benefit received [8,9]. (See 'Rationale for vaccination' below.)

In 2024, the United States ACIP recommended pneumococcal vaccination for all adults ≥50 years of age, based on the knowledge that the incidence of pneumococcal disease starts to increase at age 50 (figure 2) and cost-effective analyses that suggested that the reduction in IPD cases from administrating PCV21 or PCV20 to all adults ≥50 years of age would be worth the cost. It is important to note that most of the impact and predicted reduction in IPD cases within the 50 to 64 years of age group pertains to underrepresented ethnic/racial groups (eg, Alaskan natives, Native Americans, American Black population) who are disproportionately affected by IPD [10]. (See 'Cost-effectiveness' below and "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults", section on 'Risk factors for invasive disease'.)

Clinicians practicing outside of the United States should consult their national guidelines for guidance on pneumococcal vaccination, as guidelines may differ between nations. (See 'Society guideline links' below.)

Vaccine selection

Approach to adults without history of pneumococcal vaccination — The ACIP recommends the 21-valent PCV (PCV21) alone, 20-valent PCV (PCV20) alone, or 15-valent PCV (PCV15) followed by 23-valent PPSV (PPSV23) for all adults with indications for vaccination (table 3) [3]. For most adults, we suggest administering PCV21, when available, due to its broader coverage of serotypes that predominantly infect adults and the simplicity and lower cost of a single-dose vaccine. However, for patients with risk factors for serotype 4 pneumococcal disease (eg, residents of Navajo nation, or individuals living in Western United States and Canada who have substance use disorder or experience homelessness), we prefer PCV20 (or PCV15 followed by PPSV23 if PCV20 is not available) rather than PCV21 because PCV15 and PCV20 contain serotype 4. (See 'Choosing between PCV21 and PCV20' below.)

If PCV21 is not available, we engage in shared decision making with the patient to determine whether the patient should receive PCV20 (or PCV15 followed by PPSV23) or wait until PCV21 becomes available. (See 'Choosing between PCV21 and PCV20' below.)

If PCV20 is administered, the authors of this topic also choose to administer PPSV23 ≥8 weeks after PCV20 to patients at highest risk of IPD and/or meningitis (eg, immunocompromised individuals, presence of cochlear implant or CSF leak) to provide protection against serotypes present in PPSV23 that are absent from PCV20. Although PCV20 covers the majority of the serotypes implicated in IPD, there are three relatively common serotypes (9N, 20, 17F) included in PPSV23 that are not included in PCV20 (figure 3) [2].

If neither PCV21 nor PCV20 is available, PCV15 followed by PPSV23 is a recommended alternative. If PCV15 is administered, PPSV23 should be administered one year after PCV15 (or ≥8 weeks after PCV15 in patients with an immunocompromising condition, cochlear implant, or CSF leak) to provide immunity against an increased number of pneumococcal serotypes. When the series PCV15 followed by PPSV23 is completed, protection is offered to an additional three serotypes compared with the single PCV20 approach. Although it is hypothesized that the immunogenicity of pneumococcal polysaccharide vaccine (PPSV) is boosted by prior administration of pneumococcal conjugate vaccines (PCV), this booster effect has not been convincingly demonstrated [1,11].

These recommendations are based solely on measured antibody responses in patients receiving these vaccines since there are no comparative efficacy studies of these vaccine formulations.

Additional detail on vaccine efficacy and timing in specific immunocompromised patients is provided separately. (See 'Rationale for vaccination' below and "Immunizations in autoimmune inflammatory rheumatic disease in adults" and "Immunizations in adults with cancer" and "Immunizations in solid organ transplant candidates and recipients" and "Immunizations in hematopoietic cell transplant candidates, recipients, and donors".)

Approach to recipients of prior pneumococcal vaccines — The approach to complete the pneumococcal vaccination series for individuals who have already received pneumococcal vaccination depends on age and the specific vaccine they received (table 4).

●PPSV23 only – Adults who only received PPSV23 should receive PCV21 (or PCV20 if at increased risk for serotype 4 or if PCV21 is not available) at least a year after receipt of PPSV23 [3]. (See 'Choosing between PCV21 and PCV20' below.)

●PCV10/PCV13 only – Adults who only received PCV10 or PCV13 should receive PCV21 (or PCV20 if PCV21 is not available) at least a year after receipt of PCV10/PCV13 [3]. If neither PCV21 nor PCV20 are available, clinicians should engage in shared decision making with the patient regarding whether to administer PPSV23 or wait until PCV20 or PCV21 become available. If choosing to administer PPSV23, give PPSV23 at least one year after receipt of a PCV. For those at highest risk for pneumococcal disease (immunocompromised individuals, presence of cochlear implant or CSF leak) for whom waiting one year is not desirable, PPSV23 can be given at least eight weeks after receipt of conjugate vaccine (PCV10 or PCV13).

●Both PCV10/PCV13 and PPSV23

•Adults ≥65 years of age:

-Those who received both the PCV10/PCV13 and PPSV23 prior to age 65 years should receive PCV21 (or PCV20 if PCV21 is not available) ≥5 years after their last pneumococcal vaccine dose [3,12]. If neither PCV21 nor PCV20 are available, PPSV23 can be given instead.

-Those who received PCV10/PCV13 at any age and PPSV23 at ≥65 years of age, the ACIP advises shared decision-making between clinician and patient regarding whether to administer PCV21 or PCV20 ≥5 years after their last pneumococcal vaccine [3,12]. The authors of this topic prefer to administer PCV21 (or PCV20 if PCV21 is not available) ≥5 years after the patient's last pneumococcal vaccine since the benefits generally outweigh the minimal risks of an adverse vaccine reaction.

•Adults aged 19 to 64:

-For patients with chronic conditions, the ACIP does not recommend further vaccination until age 65 [12]. The authors of this topic prefer to give PCV21 (or PCV20 if PCV21 is not available) ≥5 years after last pneumococcal vaccine dose. If PCV21 and PCV20 are not available, the authors administer PPSV23 after ≥1 year has passed since last PCV10/PCV13 dose and ≥5 years have passed since last PPSV23.

-Patients at increased risk of meningitis (eg, CSF leak, cochlear implant) should receive PCV21 (or PCV20 if PCV21 is not available) ≥5 years after last pneumococcal vaccine dose [3,12]. If PCV21 and PCV20 are not available, the ACIP does not recommend further vaccination until age 65. The authors of this topic prefer to give PPSV23 ≥5 years after last pneumococcal vaccine dose if PCV21 and PCV20 are not available.

-Immunocompromised patients should receive PCV21 (or PCV20 if PCV21 is not available) ≥5 years after their last pneumococcal vaccine dose [3,12]. If neither PCV21 nor PCV20 are available, PPSV23 administered ≥8 weeks after last PCV10 or PCV13 dose and ≥5 years after last PPSV23 dose is a reasonable alternative. The ACIP recommends a total of two PPSV23 vaccine doses (≥5 years apart) for immunocompromised patients and to review vaccination recommendations once the patient turns 65 years old. Those who have received PCV10/PCV13 and two doses of PPSV23 can receive PCV21 (or PCV20 if PCV21 is not available) five years after their last pneumococcal vaccination, if available.

Choosing between PCV21 and PCV20 — There are certain situations in which PCV20 may be more effective, either because PCV21 is just not yet available or because the patient is at increased risk for serotype 4, which is covered by PCV20 (and PCV15) but not by PCV21.

●Patients at increased risk for serotype 4 pneumococcal disease – Residents of the Navajo nation and individuals residing in Western United States and Canada (eg, Alaska, California, Colorado, New Mexico, British Columbia) who have substance use disorder or experience homelessness are at increased risk for serotype 4 invasive pneumococcal disease [13-15]; serotype 4 is present in PCV15 and PCV20 but absent from PCV21. Therefore, for these patients, we prefer to administer PCV20 rather than PCV21 to provide coverage against serotype 4 disease [3,4].

●When PCV21 is not available – In situations where PCV21 is not available but PCV20 is available, we prefer to discuss with the patients the risks and benefits of waiting to vaccinate until PCV21 becomes available versus giving PCV20.

For example, in a healthy 66-year-old patient without any significant medical history, it may be reasonable to wait to vaccinate if PCV21 is likely to become available within the next year. In contrast, a patient receiving chemotherapy will likely benefit from immediate vaccination with PCV20 rather than waiting six to 12 months for PCV21 to become available.

PCV21 contains eleven serotypes known to be common causes of invasive pneumococcal disease (IPD) in adults that are absent from PCV20. The only exception is serotype 4, which is absent from PCV21 but present in PCV20 (and PCV15). The patient's comorbidities, demographics, and other risk factors, as well as the anticipated time of PCV21 availability should be considered when making the decision to wait for PCV21 or vaccinate with PCV20.

Revaccination — The approach to revaccination varies among experts and clinical practice guidelines. The United States Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) does not recommend repeated doses of pneumococcal vaccines beyond those discussed above (see 'Vaccine selection' above). In contrast, the authors of this topic offer repeat vaccination with PPSV23 every 5 to 10 years to all adults who received PPSV23 as part of their vaccine series (eg, PCV13 and PPSV23, PCV15 and PPSV23, or PCV20 and PPSV23 for patients at higher risk of invasive pneumococcal disease). While this differs from the ACIP recommendation, the authors believe the potential benefit of repeat revaccination with PPSV23 every 5 to 10 years greatly outweighs the risks. This does not apply to patients who have received PCV21.  

The authors' recommendation for revaccination every 5 to 10 years is based on in vitro studies that show waning of antibody and field studies that show waning effectiveness after vaccination with PPSV23 [16-18]. Although data on duration of antibody and effectiveness after receipt of PCV are not available beyond five years [19,20], any difference in opsonophagocytic effect between PPSV23 and PCV13 is no longer detectable after 12 months [21]. The authors suspect that no pneumococcal vaccine will provide lifetime protection and believe the potential benefits of repeat revaccination with PPSV23 every 5 to 10 years greatly outweigh the risks. Since there are no data on revaccination with PCV, the authors only revaccinate with PPSV23.

VACCINE ADMINISTRATION

Dose and route — Pneumococcal vaccines are administered intramuscularly as a 0.5 mL dose.

Administration with other vaccines — Pneumococcal vaccines generally may be given concomitantly with other nonpneumococcal vaccines [22-24]. When more than one vaccine is given, they should be administered with different syringes and at different injection sites.

Concurrent administration of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) with the influenza vaccine is safe and does not alter the effectiveness of either vaccine [25]. Concomitant administration of the 20-valent PCV (PCV20) with adjuvanted influenza vaccine (Fluad) [5] as well as BNT162b2 SARS-CoV-2 vaccine [26] have also been demonstrated to be immunogenic and safe.

SAFETY

Adverse effects — The immune response to pneumococcal vaccination can elicit a clinically apparent inflammatory response at the injection site and systemically. While most adverse effects associated with vaccination are not severe and are self-limited, all should be reported. In the United States, suspected adverse events should be reported to the Vaccine Adverse Event Reporting System (VAERS). VAERS can be contacted via the VAERS website or by telephone at 1-800-822-7967.

Injection site reactions — Injection site reactions are the most common adverse effects associated with pneumococcal vaccination in adults [22-24]. For the 23-valent pneumococcal polysaccharide vaccine (PPSV23), pain and tenderness at the injection site occur in over half of vaccinees, swelling and/or induration in approximately 20 percent, and redness in approximately 15 percent [22]. Rates are similar for pneumococcal conjugate vaccines (PCV) [23,24,27]. In some, these symptoms limit arm movement.

Injection site reactions usually resolve spontaneously over three to four days. Nonsteroidal anti-inflammatory drugs and warm compresses can help relieve pain.

Other adverse effects — Systemic symptoms (eg, fever, chills, fatigue, headache, myalgias, arthralgias) can also occur following vaccination [22-24]. While fever (temperature ≥38°C) occurs in less than 5 percent, other systemic symptoms occur frequently but are usually mild. Like injection site reactions, systemic symptoms following vaccination are self-limited.

Contraindications — Vaccination is contraindicated for patients who have a history of severe allergic reactions (eg, anaphylaxis) to either pneumococcal vaccine or any of its components (eg, diphtheria toxoid for PCV).

RATIONALE FOR VACCINATION

Burden of disease — S. pneumoniae is the leading bacterial cause of pneumonia worldwide [28]. Other manifestations of pneumococcal infection include meningitis, bacteremia of undetermined source, acute purulent sinusitis, and otitis media. These pneumococcal infections cause substantial morbidity and mortality [29]. Further discussion of the epidemiology of invasive pneumococcal disease (IPD) is found elsewhere. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults", section on 'Epidemiology'.)

Immunogenicity — The response to pneumococcal vaccine in adults is measured by the rise in antibody levels and/or serum opsonic (phagocytic) activity after vaccine administration. Antibody responses may be reported as mean immunoglobulin (Ig)G levels or opsonophagocytic titers (the dilution at which serum shows an opsonizing [phagocytic] effect). Opsonophagocytic titers are thought to be a better indication of protective immunity because IgG generated by older and more frail adults may be less effective in opsonizing pneumococci for phagocytosis compared with healthy young adults [30,31].

Mean antibody levels to pneumococcal polysaccharides increase after use of any of the vaccines described above. In large groups of adults, mean IgG levels remain slightly higher than at baseline 5 and 10 years after PPSV23, although vaccine efficacy wanes with time [17,18]. Antibody levels remain elevated for up to two years after vaccination with pneumococcal conjugate vaccines (PCV); to our knowledge, longer-range studies have not been reported for PCV.

Numerous studies have compared responses with polysaccharide and conjugate vaccines one to two months after vaccination of healthy adults [1,11,21,32,33]. IgG levels and opsonic activity are often, but not consistently, slightly higher to some but not all polysaccharides after PCV [1,21]. One study reported distinctly higher levels of opsonic activity one month after PCV when compared with pneumococcal polysaccharide vaccine (PPSV), but these differences had disappeared one year after vaccination [21].

In frail and elderly subjects, studies have also not shown a difference in immunogenic response between the two vaccine types [11,32]. One study found that six months after vaccination, IgG levels and opsonophagocytic titers were higher to 2 of 10 polysaccharides in PCV recipients and higher to two other polysaccharides in PPSV recipients [11].

In immunocompromised patients, limited data suggest PCV to be more immunogenic than PPSV23. As an example, in one randomized study of 128 patients with treatment-naïve chronic lymphocytic leukemia, better opsonic activity for 4 out of 10 serotypes was seen six months postvaccination in those who received the 13-valent PCV (PCV13) compared with PPSV23 [33].

Immunogenicity data on the 15-valent (PCV15), 20-valent (PCV20), and 21-valent (PCV21) pneumococcal conjugate vaccines are limited. Antibody levels one month postvaccination were similar for PCV15 [34,35] or PCV20 [36] compared with PCV13 and for PCV21 compared with PCV15 [37] and with PCV20 [38] for the serotypes common to all PCVs. Antibody levels to common serotypes were similar in recipients of PCV20 [39] and PCV21 [40] compared with PPSV23. In individuals with HIV, PCV15 was as immunogenic as PCV13 for common serotypes [41]; there are no similar data available for PCV20. (See "Immunizations in persons with HIV", section on 'Pneumococcal vaccine'.)

Vaccine efficacy — Vaccine efficacy is assessed by conducting randomized vaccine trials and evaluating for differences in disease incidence.

Polysaccharide vaccine — PPSV23 has been shown to be effective in preventing IPD and pneumococcal pneumonia [16,42-48]. In a meta-analysis of 18 randomized trials evaluating over 64,500 individuals, PPSV23 was found to reduce the risk of IPD, invasive (bacteremic) pneumococcal pneumonia, and noninvasive pneumococcal pneumonia by 82 percent, 74 percent, and 56 percent, respectively [49].

We regard the above results as having been valid at the time these studies were carried out. However, the degree of protection provided by PPSV23 has been debated among experts and has varied among studies. For example, some suggest that PPSV23 protects against invasive but not against noninvasive pneumococcal pneumonia [16,42-47,50-54]; others have failed to demonstrate efficacy for preventing either invasive or noninvasive disease [54-58] or for reducing mortality [48,49]. Possible reasons for the conflicting results include the low frequency of the outcomes being assessed (leading to a small number of events in studies), difficulties in accurately diagnosing nonbacteremic pneumococcal pneumonia, and use of nonvalidated diagnostic tests (which may lead to false-positive results and reduce the apparent efficacy of the vaccine). As might be expected, studies with more specific endpoints (eg, IPD caused by specific vaccine serotypes) have been more likely to demonstrate vaccine efficacy than those with less specific endpoints (eg, all-cause pneumonia, all-cause mortality) [50]. The vaccine efficacy of PPSV23 in more recent studies of IPD has ranged from 14 to 47 percent [59-64]. It is unclear why efficacy appears to be lower than it was in the past. Some studies included a substantial proportion of immunocompromised patients [59,60], others included participants >75 years of age [61], and others included patients who were many years past vaccination [62,63]. For example, in one study the mean time from vaccination to pneumococcal infection was 10.3 years [63]. The time from vaccination to pneumococcal infection is important, as immunity wanes over time after vaccination. In one study of adults ≥75 years of age, vaccine effectiveness declined from 74 percent within the first year after receiving PPSV23 to 15 percent five years postvaccination [61]. In another study, PPSV23 vaccine effectiveness decreased from 41 percent within two years of vaccination to 23 percent five years after vaccination [59]. Similar studies have not been done for PCV. (See 'Revaccination' above.)

Conjugate vaccines — PCV are effective against IPD and nonbacteremic pneumonia. In a large, randomized trial (CAPiTA) of over 84,000 Dutch adults ≥65 years old who received either PCV13 or placebo, PCV13 showed efficacy of 75 percent (95% CI 41-91 percent) against vaccine-type IPD, 46 percent (95% CI 22-63 percent) against vaccine-type pneumococcal pneumonia, and 45 percent (95% CI 14-65 percent) against vaccine-type nonbacteremic pneumococcal pneumonia [65]. Efficacy persisted for the duration of the trial (mean follow-up was four years).

The CAPiTA trial did not compare PCV13 with PPSV23, hence, its results cannot be extrapolated to make conclusions about the efficacy of PCV versus PPSV23 in adults. At the time this study was begun in Holland: (1) almost no adults had previously received any pneumococcal vaccine; (2) use of PCV in children was just beginning, meaning that it was a vaccine-naïve population; and (3) the investigators excluded patients who had any immunocompromising condition or medication. Further, they excluded anyone who developed an immunocompromising condition during the trial from the final data analysis (eg, patients who were later found to have a hematologic malignancy, patients who started glucocorticoids, etc). When results in patients who became immunocompromised after having been vaccinated were separately analyzed, no benefit of PCV was demonstrated (22 cases of pneumococcal disease in vaccine recipients versus 24 cases in placebo recipients). These results suggest that the pneumococcal vaccine may not be as effective in preventing IPD in immunocompromised patients.  

A study comparing 7-valent PCV (PCV7) with placebo in Malawi showed efficacy of PCV7 against pneumonia over a five-year follow-up period in adults (many with acquired immunodeficiency syndrome [AIDS]) who had previously had pneumococcal pneumonia [66]. Another study reported around 70 percent efficacy for PCV13 against community-acquired pneumonia [62].

Vaccine coverage against circulating serotypes — Serotypes that cause pneumococcal disease continue to change as new conjugate vaccines are added to children's immunization programs. This is due to a reduction in PCV-serotype nasopharyngeal colonization rates in children, leading to herd immunity and reduced incidence of disease caused by those serotypes among the entire population (including adults). Consequently, as vaccine serotypes disappear from the community, other nonvaccine serotypes take their place. These two population-level phenomena (indirect effect [or herd immunity] and emergence of replacement strains) are discussed below.

In an important study of isolates from persons with IPD in 2017, 31.2 percent were non-PCV13 serotypes covered by PCV20; however, 14 percent were non-PCV20 serotypes [2,13]. In 2018 to 2019, of serotypes recovered from adults with IPD, only 27 to 30 percent were included in PCV13. An additional 13 to 15 percent were included in PCV15, 27 to 28 percent in PCV20, and 35 to 43 percent in PPSV23 [5]. In a prospective study of 1482 adults with pneumococcal pneumonia, 37 percent of cases were due to PCV13 serotypes and an additional 27 percent and 8 percent were due to serotypes unique to PCV20 and PPSV23, respectively (figure 3) [67].

PCV21 contains eleven unique serotypes that are absent in PCV20 but caused 32 to 38 percent of IPD cases in the United States from 2018 to 2022 [4]. Analysis demonstrated that PCV21 would have provided protection against 77 to 85 percent of those IPD cases compared with 54 to 62 percent protection with PCV20. Based on these findings, PCV21 should be a substantially more effective vaccine than PCV20. However, PCV21 does not include serotype 4 which is included in all other PCV formulations and in PPSV23; after almost having been eliminated as a cause of IPD, serotype 4 has reappeared in persons who experience homelessness and in Alaskan natives [13]. (See 'Choosing between PCV21 and PCV20' above.)

It is worth noting that, while all of these vaccines contain type 3 and type 19A capsular polysaccharide, for unknown reasons they have only a minimal protective effect and these two types continue to cause nearly 20 percent of invasive pneumococcal infection.

Role of indirect effect (herd immunity) — Pneumococcal conjugate vaccines owe its success to its ability directly to prevent infection in vaccinated individuals and indirectly to reduce contagion in the population by reducing nasopharyngeal colonization rates (termed "indirect effect" or "herd immunity"). As a result of herd or indirect immunity, the epidemiology of pneumococcal disease and the effectiveness of PCV in adults are all affected by vaccination programs that are in place for children. This important factor needs to be considered in evaluating recommendations for administering PCV to adults. (See 'Vaccine selection' above.)

When PPSV23 was first marketed, it contained capsular polysaccharides from serotypes that caused nearly 90 percent of all pneumococcal disease in adults. This number has declined to about 40 percent following the introduction of PCV.

When the first PCV appeared (PCV7 [no longer marketed]) it contained capsular polysaccharides from serotypes that caused about 50 percent of all pneumococcal disease in adults. Widespread use of this vaccine in infants and toddlers eliminated carriage of these strains in vaccine recipients which was followed by a near-disappearance of these strains in adults (figure 4) [68-72], illustrating the indirect effect of the vaccine. The same result has followed the use of PCV13, except for certain serotypes (such as type 3) against which the vaccine, for undetermined reasons, provides little protection. Thus, by eight years after introduction of PCV13 for children, serotypes covered by PCV13 accounted for no more than 30 percent of IPD in adults (figure 1). Because the reduction of PCV13 strain-related illness in adults is primarily attributable to the overall reduction in circulation of PCV13 strains due to widespread vaccination in children [1,73-75], the rationale for vaccinating any immunocompetent older adults with a conjugate vaccine becomes less clear. We suspect the same phenomenon will be seen after PCV20 becomes widely used in the pediatric population.

Role of replacement strains — Vaccination with PCV and the subsequent reduction in nasal carriage of PCV serotypes appears to create an ecologic niche for nonvaccine serotypes, mostly among children [50]. The widespread use of pneumococcal conjugate vaccines has caused the emergence of "replacement strains," a term used to describe nonvaccine pneumococcal serotypes that have appeared as colonizers of the nasopharynx and as a cause of pneumococcal disease [76]. As an example, S. pneumoniae type 19A (not included in PCV7) emerged as the most common cause of pneumococcal disease in children and adults a few years after universal vaccination with PCV7 began in the United States (figure 4) [71,77]. Several other serotypes have greatly increased in prevalence since the introduction of PCV13 [2,78-80].

The epidemiologic problem that results is that the use of vaccines that contain protein-conjugated capsular polysaccharides creates a moving target and other approaches to vaccination need to be sought. (See 'Investigational approaches' below.)

COST-EFFECTIVENESS — 

Administration of PCV21 or PCV20 for all adults ≥50 years old in the United States was not cost-saving in cost-effectiveness models, but did improve health of the population [10]. For PCV21 for all adults aged ≥50 years, cost estimates ranged from $131,000 to $425,000 per quality-adjusted life-year (QALY) gained. For PCV20 for all adults aged ≥50 years, cost estimates ranged from $251,000 to $879,000 per QALY gained. A cost-effectiveness analysis for PCV21 showed the vaccine to be cost saving to $58,000 per QALY gained for the ≥65 years of age-based indication and cost saving in all models for the current risk-based indications [4]. In general, cost-effectiveness models demonstrate PCV21 to be more cost-effective than PCV20.

The expected decline in disease due to PCV21 and PCV20 types in adults once these conjugate vaccines are recommended for widespread use in infants and toddlers will almost certainly render the use of both these vaccines in adults less cost-efficient. (See 'Role of indirect effect (herd immunity)' above.)

INVESTIGATIONAL APPROACHES — 

Data suggest that the best approach for new vaccines might be to target virulence factors other than the pneumococcal capsule [81]. Existing pneumococcal vaccines utilize capsular polysaccharides as antigens. Vaccines cannot include all serotypes, replacement strains appear, and pneumococci readily acquire deoxyribonucleic acid (DNA) from other microorganisms by transformation, giving them the ability to switch capsular serotypes.

These facts have led to attempts to develop vaccines based on highly conserved proteins (eg, pneumolysin, histidine triad protein D, surface proteins A [82] and C), some of which are surface expressed and one of which (pneumolysin) contributes substantially to the pathogenesis of pneumococcal disease. Several such vaccines are in development [50,68,83-86].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pneumococcal vaccination" and "Society guideline links: Immunizations in adults".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education artic^les that ^are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Vaccines for adults (The Basics)" and "Patient education: What you should know about vaccines (The Basics)")

●Beyond the Basics topic (see "Patient education: Pneumonia prevention in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Rationale for vaccination − Pneumococcal infections (eg, pneumonia, bacteremia, meningitis) are an important cause of morbidity and mortality in adults, especially among older adults (figure 2) and those with certain conditions (eg, immunocompromising conditions, asplenia). Vaccines are effective at reducing the morbidity and mortality associated with pneumococcal disease. (See 'Introduction' above and 'Rationale for vaccination' above.)

●Types of vaccines − Two types of pneumococcal vaccines are approved and have defined indications for use in the United States (table 1) (see 'Vaccine types' above):

•A pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Pnu-Immune) that includes 23 partially purified capsular polysaccharide antigens (table 2). (See 'Polysaccharide vaccines' above.)

•Pneumococcal conjugate vaccines (PCV) − 13-valent PCV (PCV13; Prevnar 13), 15-valent PCV (PCV15; Vaxneuvance), 20-valent PCV (PCV20; Prevnar 20), and 21-valent PCV (PCV21; Capvaxive) contain capsular polysaccharide antigens covalently linked to a nontoxic protein (table 2). (See 'Conjugate vaccines' above.)

●Indications for pneumococcal vaccination − We recommend pneumococcal vaccination for all adults ≥65 years old and adults <65 years old who are at risk for pneumococcal infection or severe complications from pneumococcal infection (table 3) (Grade 1B). We also suggest pneumococcal vaccination for all adults between 50 to 64 years of age (Grade 2C). (See 'Indications for vaccination' above and 'Vaccine efficacy' above.)

●Approach to vaccine selection − The United States Centers for Disease Control (CDC) and Prevention Advisory Committee of Immunization Practices (ACIP) recommends administration of PCV21 or PCV20 alone or PCV15 in series with PPSV23 for all patients with an indication for pneumococcal vaccination (table 3).

•Adults without history of pneumococcal vaccination – For most patients who have not received prior pneumococcal vaccines, we suggest PCV21 (Grade 2C), although PCV20 alone or PCV15 followed by PPSV23 are reasonable alternatives. However, for patients at increased risk for serotype 4 pneumococcal disease (eg, residents of Navajo nation, individuals living in Western United States and Canada who have substance use disorder or experience homelessness), we prefer PCV20 (or PCV15 followed by PPSV23 if PCV20 is not available) rather than PCV21 because PCV15 and PCV20 contain serotype 4.

If PCV21 is not available, we engage in shared decision making with the patient to determine whether the patient should receive PCV20 (or PCV15 followed by PPSV23) or wait until PCV21 becomes available. (See 'Approach to adults without history of pneumococcal vaccination' above and 'Choosing between PCV21 and PCV20' above.)

•Recipients of older pneumococcal vaccines – For recipients of older pneumococcal vaccines (eg, PCV10, PCV13, PPSV23), a suggested approach is outlined in the following tables based on age (table 4). (See 'Approach to recipients of prior pneumococcal vaccines' above.)

●Revaccination − The approach to revaccination varies among experts and clinical practice guidelines. The authors of this topic revaccinate all patients who receive PPSV23 as part of their vaccine series (eg, PCV10/13 and PPSV23, PCV15 and PPSV23, or PCV20 and PPSV23) with PPSV23 every 5 to 10 years. While this differs from the CDC ACIP recommendation, the authors believe the potential benefit of repeat revaccination with PPSV23 every 5 to 10 years greatly outweighs the risks. (See 'Revaccination' above.)

●Adverse effects − Injection site reactions (tenderness, redness, swelling at site) are the most common adverse effects associated with pneumococcal vaccination in adults and are typically mild. Most are self-limited and resolve within a few days of vaccination. Warm compresses and nonsteroidal anti-inflammatory drugs can help with symptom relief. (See 'Adverse effects' above.)

●Contraindications − Vaccination is contraindicated for patients who have a history of a severe allergic reactions (eg, anaphylaxis) to either pneumococcal vaccine or any of its components (eg, diphtheria toxoid for PCV). (See 'Contraindications' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Elaine Tuomanen, MD and Patricia Hibberd, MD, PhD who contributed to earlier versions of this topic review.

UpToDate also gratefully acknowledges John G Bartlett, MD, who contributed on earlier versions of this topic review and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.