The Evolution of Pneumococcal Vaccines and Current Guidelines

SupplementsJuly 2022 Influenza Supplement

Pharmacists are in an excellent position to educate and counsel patients on current recommendations.

Streptococcus pneumoniae is an infectious pathogen associated with considerable morbidity and mortality. It is a gram-positive, anaerobic organism that has more than 100 documented serotypes.1 S pneumoniae is the most common pathogen responsible for the development of pneumonia, and it is also associated with other infections (eg, otitis, sinusitis).2

Between 2018 and 2019, the incidence of invasive pneumococcal disease (IPD) was 24 cases per 100,000 in patients aged 65 years and older.3 IPD can present as pneumonia, meningitis, or bacteremia.1

Adults who are at least 65 years old and those with certain immunocompromising conditions are at increased risk of developing IPD. In children younger than 2 years, S pneumoniae accounts for 25% to 30% of pneumonia cases and 40% of bacteremia cases. In children younger than 5 years, it is the leading cause of bacterial meningitis.

Routine pneumococcal vaccination is associated with a marked reduction in the rate of S pneumoniae infections.4 Capsular polysaccharides on the surface of pneumococci play a key role in the pathogenicity of S pneumoniae; they and are used to classify serotypes.1 The first pneumococcal polysaccharide vaccine (PPSV) was licensed in the United States in 1977, and it covered 14 serotypes. The current pneumococcal polysaccharide vaccine (PPSV23) was approved in 1983 as a replacement for the 14-valent vaccine; it covers 23 serotypes. The antibody response to PPSV23 has shown to be poor in children younger than 2 years due to the immaturity of the infant immune system; therefore, its use is not recommended in this age group.5 Pneumococcal conjugate vaccines (PCV) join serotypes to a nontoxic variant of the diphtheria toxin. The first PCV, approved in 2000, covered 7 serotypes (PCV7). In 2010, PCV7 was replaced with the 13-valent vaccine, PCV13.1

From 2018 to 2019, the 13 serotypes represented in the PCV13 were responsible for 27% of IPD cases in adults aged 65 years and older, whereas additional serotypes unique to PPSV23 accounted for 35% of IPD cases. In adults aged 19 to 64 years with underlying conditions, the serotypes in the PCV13 accounted for 30% of IPD cases, whereas additional serotypes unique to PPSV23 accounted for 43% of cases.3

In 2021, two additional PCVs were approved: PCV15 and PCV20.3 The addition of serotypes unique to PCV15 and PCV20 should improve protection from IPD in adults aged 65 years and older and in those aged 19 to 64 years with underlying conditions. This protective advantage coupled with associated cost savings in patients at least 65 years of age led the Advisory Committee on Immunization Practices (ACIP) at the CDC to recommended PCV15 or PCV20 instead of PCV13 in these populations.

Composition of PCV15 and PCV20

PCV15 and PCV20 are single-dose vaccinations.6,7 Both are indicated for the prevention of pneumonia and IPD caused by S pneumoniae. PCV15, available as the brand name product Vaxneuvance (Merck Sharp & Dohme Corp), is a preservative-free sterile suspension of purified capsular polysaccharides from 15 S pneumoniae serotypes.6 The vaccine also contains a genetically detoxified diphtheria toxin, Corynebacterium diphtheriae CRM197 protein, as a carrier protein.6 It is indicated for use in individuals 6 weeks of age and older. PCV20, available as brand name Prevnar 20 (Wyeth Pharmaceuticals LLC), also is a sterile suspension that contains saccharides of the capsular antigens from 20 S pneumoniae serotypes along with a CRM197 carrier protein.7 It is indicated for use in adults (aged ≥ 18 years).

When compared with PCV13, PCV15 contains 2 additional serotypes that account for about 15% of IPD cases in adults aged 65 years and older. Similarly, when compared with PCV13, PCV20 contains 7 more unique serotypes that are associated with approximately 27% of IPD cases.3 PCV20 contains 3 fewer serotypes than does PPSV23; however, PCVs generally induce a more robust immune response as compared with the transient protection provided by PPSV23.8,9 Details regarding specific serotype composition can be found in the Table 1.8

Efficacy of PCV15 and PCV20

The FDA approval of these 2 vaccines was based on findings from randomized controlled trials comparing antibody responses after administration of the preexisting PCV13 and PPSV23. Studies evaluated the immunogenicity of PCV15 compared with that of PCV13 in various populations, including healthy adults aged at least 50 years, adults aged 18 to 49 years at increased risk for pneumococcal disease (including Native Americans, who are at higher risk of IPD than the general population), and adults aged at least 18 years with HIV infection.3,10-12 Results from these studies demonstrated comparable or higher antibody responses with PCV15 than with PCV13 among the shared serotypes.10-12

Individuals who receive PCV13 or PCV15 should receive a dose of PPSV23; generally, it is given 1 year later.3 PPSV23 offers additional coverage against serotypes that can cause IPD. In studies in which patients received PCV13 or PCV15 followed by PPSV23, those receiving PCV15 demonstrated immune responses for all 15 serotypes, and immunogenicity was comparable among the shared serotypes with PCV13.3,11-13 Studies evaluating PCV20 versus PCV13 showed comparable immune responses for all shared serotypes, with PCV20 being associated with a slightly lower percentage of seroresponders for 2 serotypes.14,15 In studies comparing PCV20 with PPSV23, those administered PCV20 had numerically higher antibody titers and a greater percentage of seroresponders to the majority of shared non-PCV13 serotypes.9,14

Economic models assessing the cost-effectiveness of PCV20 or PCV15 followed by PPSV23 in adults aged 65 years and older determined cost savings.3 These findings of similar immunogenicity coupled with comparable safety profiles and potential cost savings led to the current ACIP pneumococcal vaccine recommendations of PCV15 and PCV20 for adults aged at least 65 years and those aged 19 to 64 years with certain underlying medical conditions or risk factors.

2022 ACIP Recommendations

The ACIP recommends PCV15 or PCV20 for PCV-naïve adults who are aged 65 years or older and those aged 19 to 64 years who have certain underlying conditions or risk factors (eg, immunocompromising conditions, alcoholism, lung disease).3 If PCV15 is used, a dose of PPSV23 should be administered at least 1 year later. A minimum interval of 8 weeks can be considered for adults with a cochlear implant, cerebrospinal fluid leak, or immunocompromising conditions (eg, chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplant, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies). Pneumococcal vaccine recommendations for adults based on different clinical scenarios are outlined in the Table 2.3

In pediatric patients, a 3-dose primary series of PCV13 is recommended as routine vaccination at 2 months, 4 months, and 6 months of age; a booster dose is recommended at 12 to 15 months of age. The ACIP recommends that children aged 6 to 18 years who have certain medical conditions and have not received a pneumococcal vaccine be given 1 dose of PCV13 followed 8 weeks later by 1 dose of PPSV23. A second dose of PPSV23 is recommended 5 years after the first dose for children with anatomic or functional asplenia, HIV infection, or other immunocompromising conditions. Children aged 6 to 18 years who already received 1 dose of PPSV23 should be given 1 dose of PCV13 eight weeks after the last PPSV23 dose.16 If a second PPSV23 dose is indicated, it should be administered at least 5 years after the last PPSV23 dose. Children should not receive more than 2 doses of PPSV23 before they are 65 years old. The use of PCV15 and PCV20 in children is under review. During its June 22-23, 2022 meeting, the ACIP approved a recommendation to use PCV15 as an option to PCV13 in children younger than 19 years and according to currently recommended PCV13 dosing and schedules.17 The recommendations will become official once they are published in the Morbidity and Mortality Weekly Report.

Administration and Storage of PCV15 and PCV20

PCV15 and PCV20 are supplied in 0.5-mL prefilled syringes. Both vaccines are delivered intramuscularly as a single dose. Prior to administration, the syringe should be held horizontally and shaken vigorously until the suspension inside appears homogeneous. In the event that the vaccine cannot be resuspended, or if discoloration or particulate matter is observed, the vaccine should not be used.6,7

Vaccines should be stored in the refrigerator at temperatures of 36 °F to 46 °F and should not be frozen.6,7 Storage of syringes horizontally may minimize resuspension time. PCV15 must be protected from light.6

Safety of PCV15 and PCV20

Adverse events (AEs) associated with the use of PCV15 and PCV20 are similar and include injection-site pain, swelling, erythema, fatigue, muscle pain, joint pain, and headache.6,7 Contraindications to these vaccines include severe allergic reaction (eg, anaphylaxis) to any component of PCV20 or PCV15 or to diphtheria toxoid. Safety and immunogenicity data on PCV20 are not available for immunocompromised individuals, and vaccination should be considered on an individual basis.7 Any AEs noted from these vaccinations should be reported to the Vaccine Adverse Event Reporting System (,7

Counseling Points

Prior to administering pneumococcal vaccines, patients should be educated about potential AEs associated with these vaccinations. Recipients also should be given the Vaccine Information Statement that is available on the CDC website ( html); it contains information about the vaccine’s purpose, indication, possible AEs, and other safety considerations.2


S pneumoniae may cause IPD, which can lead to hospitalization and death. PCV13 and PPSV23 have reduced IPD in both the pediatric and adult population. The use of PCV20 alone or PCV15 with PPSV23 should continue to reduce both invasive and noninvasive disease in patients. Pharmacists are in an excellent position to educate and counsel patients on current recommendations. They also can play a role in vaccine advocacy and help patients overcome barriers related to vaccination.

About the Authors

Nicole Rudawsky, PharmD, BCPS, is a clinical assistant professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy at Rutgers University in New Brunswick, New Jersey, and an internal medicine clinical pharmacist at Morristown Medical Center in Morristown, New Jersey.

Rupal Mansukhani, PharmD, is a clinical associate professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy at Rutgers University in New Brunswick, New Jersey, as well as a transitions of care pharmacist at Morristown Medical Center in Morristown, New Jersey.


  1. Gierke R, Wodi PA, Kobayashi M. Pneumococcal disease. Centers for Disease Control and Prevention. Reviewed August 18, 2021. Accessed June 15, 2022.
  2. Pneumococcal conjugate VIS. Centers for Disease Control and Prevention. February 4, 2022. Accessed June 15, 2022. hcp/vis/vis-statements/pcv.html
  3. Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. adults: updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(4):109-117. doi:10.15585/mmwr.mm7104a1
  4. Two new pneumococcal vaccines-Prevnar 20 and Vaxneuvance. JAMA. 2021;326(24):2521-2522. doi:10.1001/jama.2021.22119
  5. Westerink MAJ, Schroeder HW Jr, Nahm MH. Immune responses to pneumococcal vaccines in children and adults: rationale for age-specific vaccination. Aging Dis. 2012;3(1):51-67.
  6. Vaxneuvance. Prescribing information. Merck Sharp & Dohme Corp; 2022. Accessed July 6, 2022. pi_circulars/v/vaxneuvance/vaxneuvance_pi.pdf
  7. Prevnar 20. Prescribing information. Wyeth Pharmaceuticals LLC; 2021. Accessed June 15, 2022.
  8. Ask the experts. Pneumococcal vaccines. Updated and reviewed March 22, 2022. Accessed May 24, 2022. https://www.immunize. org/askexperts/experts_pneumococcal_vaccines.asp
  9. Hurley D, Griffin C, Young M, et al. safety, tolerability, and immunogenicity of a 20-valent pneumococcal conjugate vaccine (PCV20) in adults 60 to 64 years of age. Clin Infect Dis. 2021;73(7):e1489-e1497. doi:10.1093/cid/ciaa1045
  10. Stacey HL, Rosen J, Peterson JT, et al. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV-15) compared to PCV-13 in healthy older adults. Hum Vaccin Immunother. 2019;15(3):530-539. doi:1 0.1080/21645515.2018.1532249
  11. Hammitt LL, Quinn D, Janczewska E, et al. Immunogenicity, safety, and tolerability of V114, a 15-valent pneumococcal conjugate vaccine, in immunocompetent adults aged 18-49 years with or without risk factors for pneumococcal disease: a randomized phase 3 trial (PNEU-DAY). Open Forum Infect Dis. 2021;9(3):ofab605. doi:10.1093/ofid/ofab605
  12. Mohapi L, Pinedo Y, Osiyemi O, et al. Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in adults living with HIV. AIDS. 2022;36(3):373-382. doi:10.1097/QAD.0000000000003126
  13. Song JY, Chang CJ, Andrews C, et al. Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged ≥50 years: a randomized phase III trial (PNEU-PATH). Vaccine. 2021;39(43):6422-6436. doi:10.1016/j.vaccine.2021.08.038
  14. Essink B, Sabharwal C, Xu X, et al. 3. Phase 3 pivotal evaluation of 20-valent pneumococcal conjugate vaccine (PCV20) Safety, tolerability, and immunologic noninferiority in participants 18 years and older. Open Forum Infect Dis. 2020;7(suppl 1):S2. doi:10.1093/ofid/ofaa417.002
  15. Klein NP, Peyrani P, Yacisin K, et al. A phase 3, randomized, double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age. Vaccine. 2021;39(38):5428-5435. doi:10.1016/j. vaccine.2021.07.004
  16. Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2013;62(25):521-524.
  17. Advisory Committee on Immunization Practice (ACIP). Meeting recommendations. Centers for Disease Control and Prevention. Accessed July 6, 2022.
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