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).

Conjugate vaccines — PCVs consist of pneumococcal capsular polysaccharides covalently linked (conjugated) to a protein. Since these were first developed for pediatric use, earlier formulations included serotypes that caused the most disease in children. More recent formulations have selected serotypes that commonly cause disease in adults (table 2). Different carrier proteins have been used for conjugation, the most common being CRM197, a nontoxic, genetically altered variant of diphtheria toxin.

Available PCV formulations include the 10-valent PCV (PCV10; Synflorix), the 13-valent PCV (PCV13; Prevnar 13), the 15-valent PCV (PCV15; Vaxneuvance), and the 20-valent PCV (PCV20; Prevnar 20), with the numbers indicating the number of pneumococcal capsule types included in the vaccine. The 7-valent PCV (PCV7; Prevnar 7) is an older formulation that is no longer produced.

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 transmission decreases and thus lends protection to unvaccinated individuals (including adults) (figure 1). As a result, with the exception of serotypes against which the vaccines are not effective, serotypes present in PCV7 and then 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 [1]. 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 pneumonia. In agreement with the ACIP [1], we recommend pneumococcal vaccination for (table 3):

●All adults ≥65 years of age

●Adults aged 19 to 64 years with:

•Predisposing chronic medical conditions (eg, chronic lung disease, chronic liver disease, 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 (functional or anatomic asplenia, chronic renal disease, and 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. In 2018, approximately 43 percent of IPD occurred in those over the age of 65 and another 48 percent in adults <65 years of age with predisposing conditions (figure 2) [2]. While there is evidence that many patients with immunocompromising conditions such as lymphoma or multiple myeloma are unlikely to develop antibody following vaccination with pneumococcal conjugate vaccines (PCV) or pneumococcal polysaccharide vaccine (PPSV), the potential benefits of even suboptimal responses greatly outweigh the risks and the cost is regarded as appropriate for the benefit received [3,4]. (See 'Rationale for vaccination' below.)

Vaccination is not recommended for healthy adults less than 65 years of age. Although the risk for pneumococcal disease starts to increase at age 50 (figure 2), analyses have suggested initiating vaccination at that age would not be cost-effective; thus, the ACIP did not lower the recommended age for vaccination in healthy adults [5].

Vaccine selection

Approach to healthy older adults and those with predisposing medical conditions — The ACIP recommends the 20-valent PCV (PCV20) alone or the 15-valent PCV (PCV15) followed by the 23-valent PPSV (PPSV23) for all adults with indications for vaccination (table 3). For most adults, including healthy older adults, those with predisposing medical conditions, and those with a history of IPD, we prefer to administer PCV20, when available, due to the simplicity and lower cost of a single-dose vaccine. Comparative efficacy of these two approaches is unknown.

If PCV20 is not available, PCV15 followed by PPSV23 is a recommended alternative. If PCV15 is administered, PPSV23 should be administered one year after PCV15 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 PPSV is boosted by prior administration of PCV, this booster effect has not been convincingly demonstrated [6,7].

Some experts may prefer PCV15 followed by PPSV23 to PCV20 alone based on indirect preliminary data suggesting PCV15 may be more immunogenic than PCV20 [8] (but the data only demonstrate immunogenicity for the first 30 days post-vaccination) and because PCV15 has been studied in immunocompromised individuals (eg, patients with HIV) [8,9]. No study to date has directly compared PCV15 and PCV20, and the clinical significance of higher antibody levels 30 days after vaccination is unknown.

Approach to individuals at highest risk of pneumococcal disease — For immunocompromised individuals (eg, transplant recipients, persons with HIV) and those at increased risk for meningitis (eg, cochlear implant, CSF leak), the authors prefer to administer PCV20 followed by PPSV23 ≥8 weeks later. This recommendation differs from the ACIP and other experts’ recommendations to administer PCV20 alone (or PCV15 followed by PPSV23) in these populations. The authors administer the PPSV23 in addition to PCV20 in these individuals 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) [10].

Additional detail on vaccine efficacy and timing in specific immunocompromised patients is provided separately. (See 'Rationale for vaccination' below and "Pneumococcal immunization in adults with HIV" 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 and recipients".)

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 and table 5).

●Pneumococcal polysaccharide vaccine only − Adults who have only received the PPSV23 vaccine should receive PCV20 (or PCV15 if PCV20 is not available) at least a year after PPSV23 [11].

●10-valent pneumococcal conjugate vaccine or 13-valent pneumococcal conjugate vaccine only − Adults who have only received PCV10 or PCV13 should receive PCV20 (or PPSV23 if PCV20 is not available) typically at least one year after receipt of PCV10 or PCV13 [11]. However, for those at highest risk for pneumococcal disease (immunocompromised individuals, presence of cochlear implant or CSF leak) receiving PPSV23, a shorter interval of at least 8 weeks after receipt of PCV10 or PCV13 may be used. (See 'Approach to individuals at highest risk of pneumococcal disease' above.)

●Both 10-valent pneumococcal conjugate vaccine/13-valent pneumococcal conjugate vaccine and Pneumococcal polysaccharide vaccine

•Adults ≥65 years of age:

-Those who received both the PCV10/PCV13 and PPSV23 prior to age 65 years should receive PCV20 or PPSV23 (if PCV20 is not available) ≥5 years after their last pneumococcal vaccine dose [11].

-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 PCV20 ≥5 years after their last pneumococcal vaccine [11]. The authors of this topic prefer to administer PCV20 (or PPSV23 if PCV20 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 [11]. The authors of this topic prefer to give PCV20 ≥5 years after last pneumococcal vaccine dose. If PCV20 is 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 PCV20 ≥5 years after last pneumococcal vaccine dose [11]. If PCV20 is 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 PCV20 is not available.

-Immunocompromised patients should receive PCV20 ≥5 years after their last pneumococcal vaccine dose [11]. If PCV20 is not 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 PCV20 five years after their last pneumococcal vaccination, if available.

Revaccination — The approach to revaccination varies among experts and clinical practice guidelines. The ACIP does not recommend additional 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 CDC ACIP recommendation, the authors believe the potential benefit of repeat revaccination with PPSV23 every 5 to 10 years greatly outweighs the risks.

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 [12-14]. Although data on duration of antibody and effectiveness after receipt of PCV are not available beyond five years, any difference in opsonophagocytic effect between PPSV23 and PCV13 is no longer detectable after 12 months [15]. 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 [16-18]. 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 [19]. Concomitant administration of the 20-valent PCV (PCV20) with adjuvanted quadrivalent influenza vaccine (Fluad) [1] as well as BNT162b2 SARS-CoV-2 vaccine [20] have also been demonstrated to be immunogenic and safe. The 15-valent pneumococcal conjugate vaccine (PCV15) has been demonstrated to be safe and immunogenic when given with the quadrivalent influenza vaccine (Fluarix) [17].

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 [16-18]. 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 [16]. Rates are similar for pneumococcal conjugate vaccines (PCV) [17,18]. 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 [16-18]. 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 [21]. 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 [22]. 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 — Both the 23-valent pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccines (PCV) are immunogenic in adults. Numerous studies have compared responses with polysaccharide and conjugate vaccines and demonstrated no consistent differences in immunogenicity between the two vaccine types.

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 [23,24].

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 higher than at baseline 5 and 10 years after PPSV23, although vaccine efficacy wanes with time [13,14]. Antibody levels remain elevated for up to two years after vaccination with 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 [6,7,15,25,26]. IgG levels and opsonic activity are often, but not consistently, slightly higher to some but not all polysaccharides after PCV [6,15]. One study reported distinctly higher levels of opsonic activity one month after PCV when compared with PPSV, but these differences had disappeared one year after vaccination [15].

In frail and elderly subjects, studies have also not shown a difference in immunogenic response between the two vaccine types [7,25]. 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 [7].

In immunocompromised patients, limited data suggest PCV to be more immunogenic compared with 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 [26].

Data on the 15-valent PCV (PCV15) and the 20-valent PCV (PCV20) immunogenicity are limited. Antibody levels one month postvaccination were similar for PCV15 [27,28] or PCV20 [29] compared with PCV13 for the serotypes common to all three PCVs. Similarly, antibody levels were similar to serotypes common to PCV20 and PPSV23 that are absent from PCV13 among PCV20 and PPSV23 recipients [30].

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 [12,31-37]. In a meta-analysis of 18 randomized trials evaluating over 64,500 individuals, PPSV23 was found to reduce the risk of IPD (14 versus 140 events; odds ratio [OR] 0.18, 95% CI 0.10-0.31), as well as invasive (15 versus 60 events; OR 0.26, 95% CI 0.15-0.46) and noninvasive pneumococcal pneumonia (100 versus 276 events; OR 0.46, 95% CI 0.25-0.84) [38].

We regard the above results as having been valid at the time these studies were carried out. However, the degree of protection provided by PPSV has been debated among experts and has varied among studies. For example, some suggest that PPSV protects against invasive (ie, bacteremic pneumococcal pneumonia) but not against non-IPD [12,31-36,39-43]; others have failed to demonstrate efficacy for preventing either invasive or noninvasive disease [43-47] or for reducing mortality [37,38]. 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) [39]. The vaccine efficacy of PPSV23 in more recent studies of IPD has ranged from 14 to 47 percent. It is unclear why efficacy appears to be lower than it was in the past. Some studies included a substantial proportion of immunocompromised patients [48,49], others included subjects >75 years of age [50], and others included patients who were many years past vaccination [51,52]. For example, in one study the mean time from vaccination to pneumococcal infection was 10.3 years [52]. The time from vaccination to pneumococcal infection is important, as immunity wanes over time with PPSV23. 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 [50]. In another study, PPSV23 vaccine effectiveness decreased from 41 percent within two years of vaccination to 23 percent five years after vaccination [48]. Similar data are not available for PCV.

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 [53]. Efficacy persisted for the duration of the trial (mean follow-up was four years).

The CAPiTA trial did not compare PCV13 with PPSV23 arm, hence, its results cannot be extrapolated to make conclusions on the improved efficacy of PCV over PPSV23 in adults. Additionally, the context for CAPiTA needs to be outlined. 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). 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).

Another important study comparing the 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 [54]. A more recent study reported around 70 percent efficacy for PCV13 against community-acquired pneumonia [51].

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 a 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. In 2018 to 2019, of the serotypes recovered from adults >18 years with IPD, 27 to 30 percent were included in PCV13. An additional 13 to 15 percent in PCV15, 27 to 28 percent in PCV20, and 35 to 43 percent in PPSV23 [1]. In a prospective study of 1482 adults with pneumococcal pneumonia, 37 percent 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) [55].

These data help to explain why we prefer PCV20 to PCV15 and why we recommend PPSV23 after PCV20 for those persons at highest risk of pneumococcal infection. 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) — The PCV owes 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) [56-60], illustrating the indirect effect of this 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 [6,61-63], 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 [39]. 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 [64]. 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) [59,65]. Several other serotypes have greatly increased in prevalence since the introduction of PCV13 [10,66,67].

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 the 20-valent pneumococcal conjugate vaccine (PCV20) alone or the 15-valent PCV (PCV15) in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all adults ≥65 years appears to be cost-effective when compared with the prior recommendations [1]. For PCV20 alone for all adults aged ≥65 years, cost-effectiveness estimates ranged from cost-saving to USD $39,000 per quality-adjusted life-year (QALY) gained. For PCV15 in series with PPSV23 for all adults aged ≥65 years, estimates ranged from cost-saving to $282,000 per QALY gained. Cost estimates of policy options for adults aged 19 to 64 years with certain underlying medical conditions ranged from USD $11,000 to USD $292,000 per QALY gained for PCV20 and from USD $250,000 to USD $656,000 for PCV15 in series with PPSV23. Although evaluated by different models, PCV20 alone was more cost-effective than PCV15 followed by PPSV23. Models included indirect effect and waning of effectiveness. The expected decline in disease due to PCV20 types in adults once this conjugate vaccine is recommended for widespread use in infants and toddlers will almost certainly render the use of PCV20 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 [68]. 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 [69] 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 [39,56,70-73].

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 in adults" 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 articles 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) − 10-valent PCV (PCV10; Synflorix), 13-valent PCV (PCV13; Prevnar 13), 15-valent PCV (PCV15; Vaxneuvance), and 20-valent PCV (PCV20; Prevnar 20) 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). Risk factors include immunocompromising conditions (eg, immunosuppressive drugs), chronic predisposing conditions (eg, chronic lung disease, tobacco use), increased risk of meningitis (eg, cerebrospinal fluid [CSF] leak, cochlear implant), functional or anatomic asplenia, and history of invasive pneumococcal disease. (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 PCV20 alone or PCV15 in series with PPSV23 for all patients with an indication for pneumococcal vaccination (table 3).

•For immunocompetent adults without increased risk for meningitis, we suggest PCV20 rather than other pneumococcal vaccines (Grade 2C). If PCV20 is unavailable, PCV15 followed by PPSV23 one year later is an alternative. Both approaches effectively protect against a high proportion of clinically relevant pneumococcal serotypes but a single-vaccine dose with PCV20 ensures adherence and is less costly. (See 'Approach to healthy older adults and those with predisposing medical conditions' above.)

•For immunocompromised individuals and those at increased risk of meningitis (eg, cochlear implants, CSF leak), the approach differs among UpToDate experts: the authors favor PCV20 followed by PPSV23 ≥8 weeks later to provide protection against serotypes present in PPSV23 that are absent from PCV20 (figure 3). If PCV20 is unavailable, PCV15 followed by PPSV23 is an alternative. The ACIP and the section editor of this topic use the same approach as in immunocompetent patients. (See 'Approach to individuals at highest risk of pneumococcal disease' above.)

•For recipients of older pneumococcal vaccines (eg, PCV10, PCV13, PPSV23), a suggested approach is outlined in the following tables based on age (table 4 and table 5). (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 (deceased), who contributed on earlier versions of this topic review and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.