What is the recommended vaccination strategy for high-risk patients using Pneumococcal Conjugate Vaccine (PCV) vs Pneumococcal Polysaccharide Vaccine (PPSV), specifically Prevnar 13 (PCV13) and Pneumovax 23 (PPSV23)?

Pneumococcal Vaccination Strategy: PCV vs PPSV

For adults ≥65 years who have never received pneumococcal vaccine, administer a single dose of PCV20 (or PCV21) as the preferred option, which completes the series without requiring PPSV23. 1, 2

Current Preferred Approach (2023-2024 Guidelines)

The landscape has shifted dramatically from the older PCV13/PPSV23 sequential strategy. The Advisory Committee on Immunization Practices (ACIP) now recommends newer conjugate vaccines (PCV20, PCV21, or PCV15) as the preferred initial vaccination for all adults ≥65 years, not PPSV23. 1, 3

For Vaccine-Naive Adults ≥65 Years

Two acceptable options exist: 1, 2, 3

• Option A (Preferred for simplicity): Single dose of PCV20 or PCV21 alone—series complete, no PPSV23 needed
• Option B: Single dose of PCV15 followed by PPSV23 ≥1 year later

The single-dose PCV20/PCV21 approach is preferred because it provides broader serotype coverage (20-21 serotypes vs 13 in older PCV13), superior T-cell dependent immune responses compared to polysaccharide vaccines, and eliminates the need for a second vaccine dose. 2, 4, 3

For Adults with Prior Vaccination History

Previously Received PPSV23 Only

Administer a single dose of PCV20, PCV21, or PCV15 ≥1 year after the last PPSV23 dose. 1, 2, 4 This completes the series—no additional PPSV23 is needed if PCV20 or PCV21 is used. 4, 3 The FDA label notes that prior PPSV23 administration (1-5 years before) may diminish immune responses to subsequent PCV20, but vaccination is still recommended. 5

Previously Received PCV13 Only

Administer a single dose of PCV20, PCV21, or PPSV23 ≥1 year after the PCV13 dose. 1, 4, 3 For immunocompetent adults, the minimum interval is ≥1 year. 2, 4 For immunocompromised adults (chronic renal failure, asplenia, HIV, malignancies, immunosuppressive therapy, transplant recipients), the interval can be shortened to ≥8 weeks. 1, 2

Previously Received Both PCV13 and PPSV23 at Age ≥65

Shared clinical decision-making is recommended regarding administration of PCV20 or PCV21 ≥5 years after the last pneumococcal vaccine dose. 1, 2 This is optional, not routine, as the series was technically complete under older guidelines. 1

High-Risk Adults Aged 19-64 Years

Immunocompromising Conditions

This includes chronic renal failure, nephrotic syndrome, asplenia, sickle cell disease, HIV, malignancies, immunosuppressive therapy, and transplant recipients. 1, 2

Recommended strategy: 1, 2

• Option A: Single dose of PCV20 or PCV21 (series complete)
• Option B: PCV15 followed by PPSV23 ≥8 weeks later (note the shorter interval for immunocompromised patients)

Critical timing difference: Immunocompromised patients require only ≥8 weeks between PCV and PPSV23 (vs ≥1 year for immunocompetent adults) due to greater urgency for protection and adequate immune priming within 8 weeks even in immunosuppressed states. 2, 3

For immunocompromised adults who received PCV13 and one dose of PPSV23 before age 65: A second PPSV23 dose may be given ≥5 years after the first PPSV23 dose. 2 Alternatively, PCV20 or PCV21 can be given ≥5 years after the last pneumococcal vaccine, which completes the series without additional PPSV23. 1, 2

Chronic Medical Conditions (Non-Immunocompromised)

This includes alcoholism, chronic heart disease, chronic liver disease, chronic lung disease, cigarette smoking, and diabetes mellitus. 1

Recommended strategy: 1, 3

• Option A: Single dose of PCV20 or PCV21 (series complete)
• Option B: PCV15 followed by PPSV23 ≥1 year later (standard interval for immunocompetent patients)

Special Populations

Cochlear Implants or CSF Leaks

These patients are treated similarly to immunocompromised patients with the shorter ≥8 week interval between PCV and PPSV23. 1, 2 They should receive PCV20, PCV21, or the PCV15/PPSV23 series. 1

Hematopoietic Stem Cell Transplant (HSCT)

Administer 3 doses of PCV20 (or PCV15), 4 weeks apart starting 3-6 months after HSCT, followed by a fourth dose ≥6 months after the third dose or ≥12 months after HSCT, whichever is later. 1 If using PCV15, follow with PPSV23 ≥12 months after HSCT only if no chronic graft-versus-host disease (GVHD). If chronic GVHD is present, give a fourth dose of PCV15 instead of PPSV23. 1

Key Timing Intervals Summary

Critical intervals to remember: 2, 3

• PCV to PPSV23 (immunocompetent adults): ≥1 year
• PCV to PPSV23 (immunocompromised adults, CSF leak, cochlear implant): ≥8 weeks
• PPSV23 to PCV: ≥1 year for all patients
• Between different pneumococcal vaccines when both previously received: ≥5 years

Important Clinical Caveats

Never co-administer PCV and PPSV23 on the same day. 2

For adults who received PPSV23 at age ≥65 years, no additional PPSV23 doses should be administered after that dose. 1, 2 The exception is if completing the series with PCV20/PCV21 after prior PPSV23, which then becomes the final pneumococcal vaccine. 2, 4

Avoid multiple PPSV23 revaccinations beyond what is recommended (maximum of 2 lifetime doses for most patients) due to uncertainty regarding clinical benefit and safety with three or more doses. 2

If vaccination history is uncertain, do not delay vaccination—use verbal history and proceed with vaccination if indicated. 2 Never withhold vaccination due to missing records. 2

For patients requiring elective splenectomy or initiation of immunosuppressive therapy, complete vaccination at least 2 weeks before surgery or therapy initiation. 2

Rationale for the Paradigm Shift

The evolution from routine PCV13 for all adults ≥65 years (2014 recommendation) to shared clinical decision-making (2019) to the current PCV20/PCV21-first approach reflects several factors: 1, 2

• Indirect protection from pediatric PCV13 programs reduced PCV13-type disease in adults to historically low levels 1
• Conjugate vaccines provide superior immunologic memory and T-cell dependent responses compared to polysaccharide vaccines 4, 3
• Broader serotype coverage with PCV20 (20 serotypes) and PCV21 (21 serotypes) compared to PCV13 (13 serotypes) 1, 3
• Simplified vaccination schedules improve adherence and reduce missed opportunities 2

The 2019 economic analyses estimated that continued PCV13 use in series with PPSV23 cost $200,000-$560,000 per quality-adjusted life year (QALY), compared to $65,000 per QALY in 2014, making it less favorable. 1 However, the newer PCV20/PCV21 vaccines with broader coverage have changed this calculus again.