Pneumococcal

Advisory Committee on Immunization Practices (ACIP) Recommendations

Infants

• All infants without contraindications should receive four doses of 15-valent pneumococcal conjugate vaccine (abbreviation: PCV15; trade name: Vaxneuvance™) or 20-valent pneumococcal conjugate vaccine (abbreviation: PCV20; trade name: Prevnar 20®)¹ , beginning no earlier than 6 weeks of age.
• The primary series of three doses is generally administered at 2, 4 and 6 months of age. A booster dose should be administered between 12-15 months of age.
• The minimum interval between doses is 4 weeks for infants under one year of age, and 8 weeks for infants at least one year of age.

Children, Adolescents and Adults

• Children 2-18 years of age who have not yet received PCV20 and who have at least one specific risk factor (e.g., anatomic or functional asplenia, including sickle cell disease and other hemoglobinopathies; cochlear implant; cerebrospinal fluid leak; immunodeficiency due to disease or therapy, including HIV infection, Hodgkin disease, leukemia, lymphoma, multiple myeloma, chronic renal failure or nephrotic syndrome, generalized malignancy, solid organ transplant, chemotherapy or steroids – for full list, see ACIP website) should receive a dose of PCV20, or a dose of pneumococcal polysaccharide vaccine (abbreviation: PPSV23; trade name: Pneumovax 23^®) at least 8 weeks after their previous dose.
• Children 6-18 years of age with at least one risk factor (see ACIP website) who have not previously received any pneumococcal conjugate vaccine should receive a dose of PCV20, or a dose of PCV15 followed by a dose of pneumococcal polysaccharide vaccine (abbreviation: PPSV23; trade name: Pneumovax 23^®) at least 8 weeks after.
• Adults 19-49 years of age with at least one risk factor (see ACIP website) should either receive a dose of PCV15, PCV20, or 21-valent pneumococcal conjugate vaccine (abbreviation: PCV21; trade name: Capvaxive™) . If PCV15 was received, it should be followed by a dose of PPSV23 at least 8 weeks later (if not already received).
• All adults at least 50 years of age who have not previously received a pneumococcal conjugate vaccine (or whose vaccination history is unknown) should receive either PCV15, PCV20, or PCV21. If PCV15 was received, it should be followed by a dose of PPSV23 at least 8 weeks later (if not already received) ^4-8.
• Adults who have only ever received PPSV23 should receive a dose of either PCV15, PCV20, or PCV21 at least one year after their last dose of PPSV23.
• When both the conjugate and polysaccharide pneumococcal vaccines are recommended for a given individual, the conjugate vaccine should be given first. ^2,6,9.

For More Information

• ACIP Recommendations: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/pneumo.html
• Vaccine Information Statement:
  • Pneumococcal Conjugate (PCV): https://www.cdc.gov/vaccines/hcp/vis/vis-statements/pcv.html
  • Pneumococcal Polysaccharide (PPSV23): https://www.cdc.gov/vaccines/hcp/vis/vis-statements/ppv.html
• Immunization Schedules: http://www.cdc.gov/vaccines/imz-schedules/index.html 

Important Information for Obstetric Providers

• Pneumococcal vaccines are not routinely recommended during pregnancy.

Disease

Streptococcus pneumoniae is a facultative anaerobic gram-positive bacterium. 92 serotypes of S. pneumoniae have been documented, classified by their antigenic polysaccharide capsules. Antibodies provide protection specific to serotype. Pneumococci are often asymptomatically carried in the respiratory tracts of healthy persons.

Pneumococcal infections can cause pneumonia, sepsis, meningitis, otitis media, bone and joint infections, sinusitis, orbital cellulitis and skin infections. Pneumonia occurs at all ages and is the most common cause of death from Streptococcus pneumoniae. The incubation period of pneumococcal pneumonia is 1-3 days and is associated with fever, rigors (in adults), pleuritic chest pain, productive cough, dyspnea, tachypnea, hypoxia, tachycardia, malaise and weakness. Pneumococcal pneumonia has a case-fatality rate of 5-7% (may be substantially higher among the elderly). Roughly 25-30% of adult patients with pneumococcal pneumonia also develop pneumococcal bacteremia, which has a case-fatality rate of about 20% (may be as high as 60% among the elderly). Pneumococcal meningitis has a case-fatality rate of about 8% among children and 22% among adults, with neurologic sequelae often persisting among survivors. Over half of all cases of bacterial meningitis in the United States are caused by pneumococci.² WHO estimates that over 1.6 million people, including 0.7-1 million children under 2 years of age, die every year from pneumococcal infections worldwide.³

Vaccine

Three pneumococcal conjugate vaccines are licensed and recommended for use in the United States: PCV15, PCV20 and PCV21. Previous versions of pneumococcal conjugate vaccines no longer in use include 7-valent (PCV7P and 13-valent (PCV13). In all pneumococcal conjugate vaccines, purified capsular polysaccharides of S. pneumoniae are conjugated to a non-toxic variant of a diphtheria toxin known as CRM₁₉₇. All pneumococcal conjugate vaccines other than PCV21 include an aluminum phosphate adjuvant. Pneumococcal conjugate vaccines differ mainly in the number of serotypes of S. pneumoniae included: PCV15 contains 15 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, 22F, 23F, and 33F) and 33F) and PCV20 contains these same 15 serotypes plus 5 more (8, 10A, 11A, 12F, and 15B).^1,2 PCV21 contains 21 serotypes (3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A,15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B); while PCV21 does not contain 7 of the serotypes in PCV20, it does contain 8 additional serotypes⁷.  The serotypes in PCV 21 cover a greater proportion of the serotypes that have caused disease in people >65 years of age as compared to PCV 20.

The pneumococcal polysaccharide vaccine licensed for use in the United States is PPSV23, which contains the purified capsular polysaccharide antigen from 23 serotypes of S. pneumoniae: 19 of the 20 serotypes in PCV20 (all except 6A), plus 4 more serotypes (2, 9N, 17F, 20).²

Contraindications and Precautions

Severe allergic reaction (e.g. anaphylaxis) to a previous dose or vaccine component is a contraindication to further vaccination with pneumococcal vaccines. Current moderate to severe acute illness is a precaution to any vaccination.²

Vaccine Effectiveness

PPSV23 is 60-70% effective against invasive pneumococcal disease caused by vaccine serotypes, although ineffective in children younger than 2 years of age. PCV13 was highly immunogenic and estimated to be over 90% effective in children against invasive pneumococcal disease caused by vaccine serotypes. In addition, PCV13 was shown to reduce nasopharyngeal carriage of vaccine serotypes, which is important in reducing the disease burden by further limiting the spread of S. pneumonia from person to person. PCV15 and PCV20 met noninferiority criteria for all shared serotypes with PCV13 in phase 3 clinical trials prior to licensure.^1,2 PCV21 met noninferiority criteria for serotypes for all shared serotypes with PPSV23 and PCV20.⁷

Vaccine Safety

Local reactions such as pain, redness and swelling occur in 30-50% of PPSV23 recipients. Moderate reactions such as fever and myalgia are uncommon (<1%) and severe adverse reactions are rare.² Cellulitis-like reactions after PPSV23  have also been reported in the literature.^10,11

Common reactions to PCV13 included local reactions such as pain (50-80%), redness (10-30%) and swelling (10-30%), with highest rates among children, followed by toddlers, then infants, then adults. Most local reactions are mild to moderate but about 8% among infants and toddlers are considered severe, for example tenderness that temporarily interfered with movement of the limb. Other common reactions include irritability among infants (<70%) and children (>20%), and fatigue (>30%), myalgia (>20%), and headache (>20%) among adults. Fever higher than 100.4°F within 7 days after vaccination was reported in 24-35% of infants and toddlers receiving PCV13 in clinical trials; high fever was reported in less than 1%. Rates of fever then decrease with age; occurring in only 6-8% of children at least 2 years of age.^2,12

Reactions among adults to PCV15, PCV20 and PCV21 are similar to PCV13. Common reactions to PCV15 include injection site pain (>70%), injection site swelling (>10%), myalgia (>50%), fatigue (>40%), and headache (>30%). Common reactions to PCV20 include injection site pain (67-76%), injection site swelling (15-22%), myalgia (27-29%), fatigue (21-34%), and headache (19-27%).^13,14 Common reactions to PCV21 include injection site pain (56%), fatigue (27%), headache (18%), and myalgia (11%).⁷

Vaccines which may induce fever may also rarely induce febrile seizures. Febrile seizures are a common and typically benign childhood condition, occurring in 2-5% of children at some point during their first five years of life. Febrile seizures have an estimated background incidence of 240–480 per 100,000 person-years in children under five years, although this varies considerably by age, genetics, co-morbidities and environmental risk factors. There are no long-term effects of simple febrile seizures, with the possible exception of an increased risk of recurrence.^15-18 Febrile seizures were estimated to occur at a rate of 5.3 per 100,000 doses in children aged 6-59 months receiving PCV13, and 17.5 per 100,000 doses after receiving PCV13 and concomitant trivalent inactivated influenza vaccine. These risk differences varied with age due to the age-dependent background rates of febrile seizures, with the highest estimates at 16 months and the lowest at 59 months.¹⁸ See the Do Vaccines Cause Seizures? summary for more details.

Considerations in Pregnancy

The safety of PPSV23 vaccine in pregnancy has not been studied. However, no adverse outcomes have been reported among newborns whose mothers were inadvertently vaccinated with PPSV23 during pregnancy. Those who are at high risk of pneumococcal disease should be vaccinated before pregnancy, if possible.²

References

1.         ACIP Updates: Recommendations for Use of 20-Valent Pneumococcal Conjugate Vaccine in Children – United States, 2023. MMWR Morbidity and mortality weekly report. Sep 29 2023;72(39):1072. doi:10.15585/mmwr.mm7239a5

2.         Epidemiology and Prevention of Vaccine-Preventable Diseases. 2015.

3.         Organization WH. Pneumococcal vaccines WHO position paper–2012. Releve epidemiologique hebdomadaire. Apr 6 2012;87(14):129-44.

4.         Matanock A, Lee G, Gierke R, Kobayashi M, Leidner A, Pilishvili T. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morbidity and mortality weekly report. Nov 22 2019;68(46):1069-1075. doi:10.15585/mmwr.mm6846a5

5.         Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices – United States, 2022. MMWR Morbidity and mortality weekly report. Sep 16 2022;71(37):1174-1181. doi:10.15585/mmwr.mm7137a3

6.         Kobayashi M, Pilishvili T, Farrar JL, et al. Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports. Sep 8 2023;72(3):1-39. doi:10.15585/mmwr.rr7203a1

7.         Kobayashi M, Leidner AJ, Gierke R, et al. Use of 21-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Practices – United States, 2024. MMWR Morbidity and mortality weekly report. Sep 12 2024;73(36):793-798. doi:10.15585/mmwr.mm7336a3

8.         CDC Recommends Lowering the Age for Pneumococcal Vaccination from 65 to 50 Years Old. October 23, 2024. https://www.cdc.gov/media/releases/2024/s1023-pneumococcal-vaccination.html

9.         Kobayashi M, Bennett NM, Gierke R, et al. Intervals Between PCV13 and PPSV23 Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbidity and mortality weekly report. Sep 04 2015;64(34):944-7. doi:10.15585/mmwr.mm6434a4

10.       von Elten KA, Duran LL, Banks TA, Banks TA, Collins LC, Collins LC. Systemic inflammatory reaction after pneumococcal vaccine: a case series. Human vaccines & immunotherapeutics. 2014;10(6):1767-70. doi:10.4161/hv.28559

11.       Huang DT, Chiu NC, Chi H, Huang FY. Protracted fever with cellulitis-like reaction in pneumococcal polysaccharide-vaccinated children. The Pediatric infectious disease journal. Oct 2008;27(10):937-9. doi:10.1097/INF.0b013e3181734fb6

12.       Food and Drug Administration. Package Insert – Prevnar 13. Updated August 2017. Accessed October 28, 2021. https://www.fda.gov/media/107657/download

13.       Food and Drug Administration. Package Insert – VAXNEUVANCE. Accessed October 28, 2021. https://www.fda.gov/media/150819/download

14.       Food and Drug Administration. Package Insert – PREVNAR 20. Updated June 2021. Accessed October 28, 2021. https://www.fda.gov/media/149987/download

15.       (AAP) AAoP. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. Feb 2011;127(2):389-94. doi:10.1542/peds.2010-3318

16.       (AAP) AAoP. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. Jun 2008;121(6):1281-6. doi:10.1542/peds.2008-0939

17.       Bonhoeffer J, Menkes J, Gold MS, et al. Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation. Vaccine. Jan 26 2004;22(5-6):557-62.

18.       Tse A, Tseng HF, Greene SK, Vellozzi C, Lee GM. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011. Vaccine. Mar 2 2012;30(11):2024-31. doi:10.1016/j.vaccine.2012.01.027