Continuing Education Activity

The advent of pneumococcal vaccines has proven to be a significant advancement in treating and preventing a widespread and sometimes deadly disease process. The pneumococcal conjugate vaccines are recommended differently depending on the patient population. While both vaccine types are proven to stimulate long-lasting antibodies in immunocompromised adults, conjugate vaccines have been shown to provide some additional benefits, as will be covered here. This activity describes the mode of action of pneumococcal vaccines, including methods of administration, formulations, adverse event profiles, eligible patient populations, and monitoring, and highlights the role of the interprofessional team in the management of these patients.

Objectives:

• Identify the types of pneumococcal viruses requiring vaccinations.
• Summarize the absolute and relative contraindications of the pneumococcal vaccine.
• Review the methods of administering pneumococcal vaccination and eligible patients for each type of vaccine.
• Explain interprofessional team strategies for improving care coordination and communication to advance pneumococcal vaccination and improve patient outcomes.

Indications

Pneumococcal vaccines are vaccines that work against the bacteria Streptococcus pneumoniae. These vaccines come in two formulations, polysaccharide vaccine, and conjugate vaccine.[1][2] The advent of pneumococcal vaccines has proven to be a significant advancement in treating and preventing a widespread and sometimes deadly disease process.[3][4] Currently, PCV13, PCV15, PPSV23, and PCV20 are used for immunization. The CDC and ACIP have revised the recommendations for routine administration of the pneumococcal conjugate vaccine, which is reflected in the administration section. In 2021, PCV20 and PCV15 were approved by the FDA for adults aged 18 years and older based on clinical trials that compared antibody responses to PCV20 and PCV15 with those to PCV13. In 2022, FDA approved expanded indications for PCV15 to include individuals aged six weeks–17 years. PCV15 is anticipated to decrease pneumococcal disease incidence in children as it induces immunity against additional pneumococcal disease-causing serotypes. The ACIP (Advisory Committee on Immunization Practices) suggests either PCV20 alone or PCV15 in series with PPSV23 for adults 65 and older and 19 to 64 years with risk factors or underlying medical conditions.[5]

PCV13 (13-valent pneumococcal conjugate vaccine): PCV 13 provides active immunization against serotypes of Streptococcus pneumoniae (1, 3, 4, 5, 6A and 6B, 7F, 9V, 14, 19A, and 19F, 18C, and 23F). Indications vary according to age.

• Children six weeks -five years of age: Prevention of IPD (invasive pneumococcal disease) caused by Streptococcus pneumoniae and for the prevention of otitis media
• Children six years through seventeen years of age: Prevention of IPD caused by Streptococcus pneumoniae
• Adults ≥18 years: Prevention of IPD and pneumonia caused by Streptococcus pneumoniae.[6]

PCV15 (15-valent pneumococcal conjugate vaccine): PCV 15 provides active immunization against serotypes of Streptococcus pneumoniae (1, 3, 4, 5, 6A and 6B, 7F, 9V, 14, 18C, 19A and 19F, 22F, 23F, and 33F). It is indicated for:

• The prevention of IPD caused by Streptococcus pneumoniae in individuals six weeks of age and older
• PCV13 and PCV15 can be used interchangeably.[7]

PCV20 (20-valent pneumococcal conjugate vaccine): PCV20 is recommended for active immunization against serotypes of Streptococcus pneumoniae (1, 3, 4, 5, 6A, and 6B, 7F, 8, 9V, 11A, 10A, 12F, 14, 15B, 18C, 19A and 19F, 22F, 23F, and 33F). 

• PCV 20 is indicated for preventing pneumonia and invasive pneumococcal diseases in adults 18 years of age and older.[8]

PPSV23 (23-valent pneumococcal polysaccharide vaccine): PPSV 23 is recommended for active immunization for preventing pneumococcal disease caused by the 23 serotypes of streptococcus pneumoniae (1, 2, 4, 3, 5, 6B, 7F, 8, 9N and 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A and 19F, 20, 22F, 23F, and 33F).

• PPSV23 is approved in individuals≥ 50 age. 
• PPSV 23 is also indicated in children≥ two years of age at high risk of pneumococcal infection.[9][10][11]

Mechanism of Action

Both vaccines promote active immunization against the serotypes of the conjugate and capsular polysaccharides contained in the formulation of the vaccine. Immunity develops approximately 2 to 3 weeks after vaccination and lasts five years. However, in children and the elderly, re-immunization may be necessary sooner.

PCV13

This vaccine formulation demonstrates improved antibody response compared to the pneumococcal polysaccharide vaccine because it contains purified capsular polysaccharides of pneumococcal serotypes conjugated to a carrier protein. PCV 13 actively immunizes against invasive disease caused by S. pneumoniae capsular serotypes 1, 3, 4, 5, 6B, 6A, 7F, 9V, 14, 18C, 19A, 19F, and 23F. All of the serotypes are individually conjugated to a CRM197 protein.[12]

PCV15

PCV15 contains polysaccharide serotypes 22F and 33F in addition to the PCV13 serotypes, conjugated to genetically detoxified diphtheria toxin. The randomized controlled trial in adults ≥50 years demonstrated that PCV15 met the noninferiority criteria compared with PCV13 for the 13 shared serotypes. PCV15 also had statistically significant responses for serotype three and PCV15-unique serotypes 22F and 33F. Another randomized controlled trial included healthy infants aged 42 to 90 days to assess the interchangeable use of PCV13 and PCV15. IgG geometric mean concentration for the 13 shared serotypes estimated was similar to those in children immunized with PCV13. In PCV-naive or partially vaccinated in the age group 7 months–17 years who received catch-up PCV doses, PCV15 elicited IgG concentrations similar to PCV13 for the 13 shared serotypes. PCV15 elicited higher IgG geometric mean concentration for 6 of 13 shared serotypes and the two unique serotypes in children with sickle cell disease. Additionally, among children with HIV infection, PCV15 produced higher IgG concentrations for two unique serotypes and 8 of 13 shared serotypes compared with PCV13.[13]

PCV20

PCV20 contains serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F, in addition to PCV13, conjugated to detoxified diphtheria toxin. PCV20 produced a strong immune response to all 20 vaccine serotypes in adults 18–49 years. PCV20 provides enhanced protection which is evident based on an opsonophagocytic activity assay.[14]

PPSV 23

This vaccine formulation is the first pneumococcal vaccine formulated from a capsular polysaccharide. PPSV 23 contains 23 capsular polysaccharide types of S. pneumoniae, representing at least 85% to 90% of pneumococcal disease isolates in the United States. It has shown a 50% to 80% efficacy in preventing invasive pneumococcal disease in adults. S. Pneumoniae serotypes are 1, 2, 3, 4, 5, 6B, 7F, 8, 9V, 9N, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.[15]

Administration

PCV 13, PCV 15, and PCV 20 are administered by IM route. PPSV 23 can be administered by IM or SC route. PCV13 and PCV15 are available in a single-dose prefilled syringe (0.5 mL). PCV13/PCV15 may be administered simultaneously with additional vaccines, including COVID-19. However, they must be prepared and administered in separate syringes and utilizing different injection locations. Vaccines should be discarded if there is the presence of particulate matter and discoloration in the solution.[16][17] Hands should be cleansed with an alcohol-based antiseptic hand rub or with soap and water before preparing vaccines for administration.[18][19][20]

Site: The deltoid muscle is the preferred location for PCV13/PCV15 vaccination in older children and PCV15/PCV20 vaccination in adults. The preferred injection site for PCV13/PCV15 for infants and young children is vastus lateralis in the anterolateral thigh.

Vaccination schedule according to CDC and ACIP

Infants and children

CDC and ACIP suggest using PCV (PCV13 or PCV15) for children (2–59 months). PCV13 and PCV15 can be used interchangeably. PCV15 is not indicated for those who have received four doses of PCV13 or age-appropriate complete PCV13 vaccination series. It is important to note that the minimum age for this first dose is six weeks for PCV13/15 and 2 years for PPSV 23. Preterm infants should be vaccinated according to chronological age regardless of birth weight.

• Infants aged 2–6 months: Four doses of pneumococcal conjugate vaccine (PCV13 or PCV15) are recommended. Administer PCV13 or PCV15 to infants in a sequence of 4 doses (3 primary and one booster). The primary series consists of 3 doses of PCV. Infants obtaining the first dose at age ≤6 months should be administered three doses of PCV at intervals of approximately eight weeks. The minimum interval is of 4 weeks. The booster(fourth) dose is advised at age 12–15 months. It should be administered ≥8 weeks after the third dose. Hence the recommended schedule is one dose of PCV 13/PCV15 at 2, 4, 6 months, and 12 to 15 months.
• Infants aged 7–11 months: If PCV is initiated at age 7 to 11 months, three doses (either PCV13 or PCV15) are advised. The first two doses should be administered with an interval of ≥4 weeks between doses. The third dose should be given at 12–15 months; an interval of ≥8 weeks between the second and third doses is advised.
• Children aged 12–23 months: If PCV is initiated at 12 to 23 months of age, two doses (either PCV13 or PCV15) are suggested, and an interval of ≥8 weeks between doses is advised.
• Children aged 24–71 months: Unvaccinated and healthy children aged 24 to 59 months be administered a single dose of PCV (PCV13 /PCV15). Unvaccinated children (24 to 71 months) with any risk condition should receive two doses of PCV (PCV13 or PCV15), and an interval of ≥8 weeks between two doses is recommended. 
• Children and adolescents aged 6–18 years with CSF leak, immunocompromising condition, or cochlear implant: If a dose of PCV13/PCV15 has not been given earlier, a single dose of PCV13 or PCV15 is advised, regardless of previously received PPSV23 or PCV7.
• Hematopoietic stem cell transplants: Recipients of stem cell transplants are advised to receive 3 PCV doses followed by a dose of PPSV23 starting 3 to 6 months after the transplant. In children with graft-versus-host disease(GVHD), PPSV23 can be substituted with a fourth dose of PCV. [5]

Children 2 to 5 Years

CDC suggests pneumococcal vaccination for medical conditions that can increase the risk of pneumococcal infection. These conditions are listed below:

• CSF leak
• Cochlear implant
• Chronic heart disease, cardiac failure, and particularly cyanotic congenital heart disease
• Chronic lung disease; asthma treated with chronic high-dose oral corticosteroids
• Diabetes mellitus

For above mentioned medical conditions CDC suggests:

• Administering two doses of either PCV13 or PCV15 if children are unvaccinated or received an incomplete pneumococcal conjugate vaccine series with <3 doses before 24 months of age. Administer the second dose at least eight weeks after the first dose.
• Give one dose of PCV13 or PCV15 if patients have been administered three doses of a PCV before 12 months but have yet to receive a fourth booster dose.
• Give one dose of PPSV23 at least eight weeks after completing the PCV series.

High-risk medical conditions are listed below:

• Chronic renal failure or nephrotic syndrome
• Sickle cell disease or other hemoglobinopathies
• Congenital immunodeficiency
• Congenital or acquired asplenia, or splenic dysfunction
• Diseases associated with the treatment of immunosuppressive drugs or radiation therapy
• Leukemia
• Solid organ transplant
• Hodgkin disease
• Lymphoma
• Malignancy
• HIV infection

For high-risk medical conditions, CDC suggests:

• Administer two doses of (PCV13 or PCV15) if patients are unvaccinated or received an incomplete pneumococcal conjugate vaccine series with <3 doses before 24 months of age. Administer the second dose at least eight weeks after the first.
• Administer one dose of PCV13 or PCV15 if they received three doses of a pneumococcal conjugate vaccine before 12 months but have yet to receive their fourth booster dose.
• Administer two doses of PPSV23 after the PCV series is complete. Give the first dose at least eight weeks after any previous PCV dose, then give the second dose of PPSV23 at least five years after the first PPSV23 dose.

Children 6 to 18 Years

For a cerebrospinal fluid leak or cochlear implant, CDC suggests

• Administer one dose of either PCV13 or PCV15 if the patients have not received any doses of a PCV vaccine. PCV13/PCV15 should be administered before PPSV23.
• Administer one dose of PPSV23 (if not already given before in childhood)≥ eight weeks after PCV13 or PCV15.

For  high-risk medical conditions mentioned above, CDC suggests

• Administer one dose of either PCV13 or PCV15 if the patients have not received any doses of a PCV vaccine. Administer PCV13 or PCV15 before giving any recommended doses of PPSV23.
• Administer two doses of PPSV23. The first dose of PPSV23 should be administered at least eight weeks after any initial PCV dose. The second dose of PPSV23 should be administered only five years after the first dose of PPSV23.

For a child with

• Chronic heart disease, cardiac failure, and particularly cyanotic congenital heart disease
• Chronic lung disease; asthma treated with chronic high-dose oral corticosteroids
• Diabetes mellitus

CDC suggests  

• Administering one dose of PPSV23 (if not already given earlier in childhood).

Adults 19 to 64 Years

CDC advises pneumococcal vaccination for adults 19-64 years old with certain chronic medical diseases or high-risk factors:

• Alcoholism
• CSF leak
• Chronic liver disease
• Chronic lung disease, including COPD and asthma
• Chronic heart disease, including CHF and cardiomyopathies
• Cigarette smoking
• Cochlear implant
• Diabetes mellitus
• Congenital or acquired asplenia*
• Congenital or acquired immunodeficiency*
• Chronic renal failure*
• Malignancy*
• Hodgkin disease*
• HIV infection*
• Iatrogenic immunosuppression from radiation therapy and chronic systemic corticosteroids*
• Lymphoma*
• Leukemia*
• Multiple myeloma*
• Nephrotic syndrome*
• Solid organ transplant*
• Sickle cell disease or hemoglobinopathies*

*Indicates immunocompromising conditions

For adults who have not been given any pneumococcal vaccine or have received only PCV7, CDC recommends

• Administer 1 dose of PCV15/PCV20.
• If PCV15 is administered to the patient, it should be followed by PPSV23 after one year. The minimum interval between 2 doses is eight weeks and is used in patients with an immunocompromising state, CSF leak, and cochlear implant.
• It is important to note that if PCV20 is administered, PPSV23 is not indicated for the patient.

For adults who have received PPSV23 only, CDC suggests

• Administer 1 dose of PCV15 or PCV20.
• The PCV15 or PCV20 dose should be given at least one year after the last PPSV23 vaccination.

For adults who have only received PCV13, CDC suggests

• Administer a single dose of PCV20 at least one year after PCV13. The second option is administering a single dose of PPSV23 at least eight weeks after the previous vaccination with PCV13.
• Patients with immunocompromising conditions require additional doses of PPSV23. The second dose of PPSV23 is administered at least five years after the first. The third dose of PPSV23 is given at ≥ 65 years (minimum interval of five years from the second dose of PPSV23). A third dose is not indicated if a patient is ≥ 65 years old when the second dose is administered.
• Patients with risk factors or medical conditions listed above will require a second dose of PPSV23 at age ≥ 65 years.

For adults who have received PCV13 and one dose of PPSV23, CDC suggests

• Administer one dose of PCV20 at least five years after the last pneumococcal vaccine.
• The minimum interval (1 year since the last PCV13 dose and five years since the last PPSV23 dose) can be considered in patients with a cochlear implant, CSF leak, or immunocompromising condition. 
• The second option is administering PPSV23 at least eight weeks after PCV13 and five years after PPSV23 if patients have immunocompromising conditions.
• Patients with an immunocompromising condition will require an additional third dose of PPSV23 at age ≥65 years. (minimum interval of five years since the second dose of PPSV23).

Adults ≥65 years of age

For adults≥ 65 years who have not been administered any pneumococcal vaccine or have received only the PCV7 vaccine, CDC suggests:

• Administer 1 dose of PCV15 or PCV20.
• If PCV15 is used, it is followed by PPSV23 at least one year later. The minimum period can be reduced to eight weeks in adults with an immunocompromising condition, CSF leak, or cochlear implant.
• If PCV20 is used, then PPSV23 is not indicated. 

For adults ≥65 years who have only received PPSV23, CDC suggests:

• Administer 1 dose of PCV15 or PCV20.
• The PCV15 or PCV20 should be administered at least one year after the PPSV23.
•  An additional dose of PPSV23 is not required.

For adults ≥65 years who have been administered only PCV13, CDC suggests two options: 

       1. Administer one dose of PCV20 at least one year after PCV13 

       2. Administer one dose of PPSV23 at least one year after PCV13. The minimum interval can be reduced to eight weeks for a CSF leak, cochlear implant, or an immunocompromising condition.

For adults ≥65 years who have been administered PCV13 regardless of age and PPSV23 before age 65 years, the CDC suggests two options:

1. Administer one dose of PCV20 at least five years after the last pneumococcal vaccine. The minimum interval (one year since the last PCV13 dose and five years since the last PPSV23 dose) is considered in patients with a cochlear implant, CSF leak, or immunocompromising condition. 
2. Administer one dose of PPSV23 at least five years after the last pneumococcal vaccine. The minimum interval (8 weeks since the last PCV13 vaccination and five years since the last PPSV23 vaccination) is considered in patients with a cochlear implant, CSF leak, or immunocompromising condition.

Shared decision-making: For adults ≥ 65 years who have been administered PCV13 at any age and PPSV23 at or after age 65 years, CDC suggests shared clinical decision-making. If the clinician and patient determine PCV20 is appropriate, PCV20 should be administered at least five years after the previous pneumococcal vaccine.

Specific Patient Populations

Hepatic Impairment: The ACIP advises pneumococcal vaccination in patients with chronic liver disease.[21]

Renal Impairment: CKD patients naive in pneumococcal immunization should be administered PCV13, followed by a dose of PPSV23 at eight weeks and 2nd dose of PPSV23 after five years.[22]

Pregnancy Considerations:  Clinical information on the safety of PCV-20 and PCV-15(conjugate vaccines) during pregnancy is inadequate. PPSV23 increases antibody titers in infants. ACOG(The American College of Obstetricians and Gynecologists) recommends PPSV23 in patients with diabetes, heart disease, sickle cell anemia, and lung disease.[23]

Breastfeeding Considerations: The CDC suggests that vaccines administered to a nursing mother do not impact breastfeeding safety for mothers or infants. Breastfeeding is not a contraindication to the administration of the pneumococcal vaccines. Immunization during the third trimester of pregnancy increases the pneumococcal antibodies in breast milk. Breastfed infants should be vaccinated as suggested by ACIP and CDC.[24]

Pediatric Patients: The safety and efficacy of PCV13 in children < 6 weeks of age have not been demonstrated.

Elderly Patients: For PPSV 23, AEFI(adverse events following immunization) is higher following revaccination compared to initial vaccination. Consequently, routine revaccination of PPSV23 in immunocompetent patients>65 years of age is not advised.

Adverse Effects

There are reports of the following adverse effects in different age groups. Following are the reports of common adverse events following immunization (AEFI).[25]

PCV13

Infants and toddlers 

• Irritability 
• Injection site tenderness 
• Decreased appetite
• Sleep alterations 
• Fever
• Injection site redness 
• Injection site swelling 

Children 5 to 17 Years

• Injection site tenderness, redness, and swelling
• Irritability
• Decreased appetite 
• Sleep alterations
• Fever 

Adults 18 Years and Older

• Pain, redness, and swelling at the injection site 
• Fatigue 
• Headache 
• Muscle pain 
• Joint pain
• Decreased appetite
• Limitation of arm movement
• Vomiting
• Fever 
• Chills
• Rash 

PCV 15

Children 2 to 15 months

• Injection-site erythema, induration, and swelling
• Irritability
• Somnolence
• Fever
• Decreased appetite

Children and adolescents 2 through 17 years of age 

• Injection-site pain, erythema, swelling, and induration
• Myalgia
• Fatigue 
• Headache 

Adults 18 years and older 

• Injection-site pain, swelling, erythema
• Fatigue 
• Myalgia 
• Headache
• Arthralgia 

PCV20

• Pain and swelling at the injection site
• fatigue 
• headache 
• muscle pain
• arthralgia

PPSV23 

• Injection site pain/soreness/tenderness  
• Injection site induration/swelling
• Headache 
• Injection site erythema
• Fatigue/weakness 
• Myalgia 

Interactions with drugs and vaccines

• Concomitant administration of PPSV23 and live zoster vaccine showed a reduced immune response to the live zoster vaccine. The recommendation is for administrations to be at least four weeks apart.[26]
• Immunosuppressive treatment: Patients on immunosuppressive therapy, including corticosteroids, chemotherapy, and radiation therapy, may have diminished seroprotection to the pneumococcal vaccine. A booster dose may be considered according to guidelines.[27]
• Antipyretics: Antipyretics blunts the immune response to some serotypes following immunization of PCV 13. However, this interaction requires significant additional research.[28]

Contraindications

PCV13 and PPSV23 contraindications include severe allergic or anaphylactic reactions to any component of the formulation of the vaccine or any diphtheria toxoid-containing vaccine. Pregnancy is not a contraindication to vaccination. Pregnant women at high risk of infection should receive the vaccination.[29] Similarly, severe allergic reactions to PCV 20 or diphtheria toxoid are contraindications to using PCV 20.

Warnings and Precautions

• PCV20: Patients with altered immunocompetence may have decreased immune responses to PCV20.
• PPSV23: Use caution in severely compromised pulmonary and cardiovascular function, as any systemic reaction can lead to significant risk to the patient.
• PCV13 and PCV15: Apnea after vaccination has been noted in premature infants. These infants should be observed for 48 hours after immunization.[30]

Monitoring

For the first 15 minutes following pneumococcal vaccine administration, patients require monitoring for allergic reactions such as anaphylaxis and syncope. Adverse events after the vaccine administration should be notified to the Vaccine Adverse Event Reporting System (VAERS).[31] For catch-up vaccination and subsequent visits, clinicians can use the PneumoRecs VaxAdvisor application developed by the CDC.[32] In addition, vaccine safety is monitored by Vaccine Safety Datalink (VSD) from electronic health records at eight healthcare systems.[33]

Toxicity

There is no overdose risk with the administration of the vaccine. Careful dosing, administration, and adherence to the vaccine guidelines should preclude any chance of overdosing. Preclinical studies demonstrated no toxicity in rats when the modified pneumococcal vaccine was administered subcutaneously three times in 2-weeks at a supratherapeutic dose.[34]

Enhancing Healthcare Team Outcomes

The pneumococcal vaccine is safe and effective and can help reduce the risk of infection with certain types of pneumonia, sepsis, and meningitis. The CDC suggests shared clinical decision-making between patients and clinicians as it has been shown to increase vaccination rates among adults.[35] All interprofessional healthcare team members, including clinicians (MDs, DOs, NPs, PAs), nursing staff, and pharmacists, should educate patients on the benefits of the pneumococcal vaccine, answer patient questions, alleviate any concerns they may have about the vaccine, and provide information for the patient in the unlikely event that they experience an adverse reaction.

Pediatricians and primary care physicians should prescribe the age-appropriate vaccine according to the latest recommendations of the CDC and ACIP. In the event of anaphylaxis, emergency medicine physicians should rapidly stabilize the patients. All healthcare team members must also ensure the patient's medical record is updated to reflect the most recent vaccine administration, especially since clinicians, nurses, and pharmacists can all administer the vaccine in most states. This integrated teamwork and information sharing will help drive improved patient outcomes related to pneumococcal vaccination. Over the years, the vaccine has proven to be safe and effective.[36] [Level 5]