Which pneumonia vaccine is recommended, PCV20 (Pneumococcal Conjugate Vaccine 20) or PCV21 (Pneumococcal Conjugate Vaccine 21)?

Pneumococcal Vaccine Selection: PCV20 vs PCV21

Both PCV20 and PCV21 are acceptable options for pneumococcal vaccination in adults, with the choice primarily determined by local serotype epidemiology—specifically, whether serotype 4 invasive pneumococcal disease (IPD) is prevalent in your community. 1

Key Difference Between PCV20 and PCV21

PCV21 does not contain serotype 4, which is included in PCV20, PCV15, and PPSV23. 1 This is the critical distinguishing factor:

• PCV21 contains 8 unique serotypes not found in previously available vaccines (serotypes 2, 9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B) 1
• PCV20 contains serotype 4 plus 7 additional serotypes beyond PCV13 (8, 10A, 11A, 12F, 15B, 22F, and 33F) 1, 2

Clinical Decision Algorithm

Step 1: Assess Geographic Risk for Serotype 4 IPD

If your patient lives in or has ties to the western United States (Alaska, Navajo Nation, Colorado, New Mexico, Oregon), strongly consider PCV20 over PCV21. 1

• Serotype 4 IPD has reemerged in these regions, with ≥30% of IPD cases caused by serotype 4 1
• Affected populations include adults <65 years with risk conditions, substance abuse history, or experiencing homelessness 1

If your patient does not live in these high serotype 4 regions, either PCV20 or PCV21 is appropriate. 1

Step 2: Apply Standard Vaccination Recommendations

The 2024 ACIP guidelines provide equivalent recommendations for both vaccines across all adult populations 1:

For Adults ≥65 Years (PCV-Naïve)

• Single dose of PCV21 OR PCV20 1, 3
• No additional pneumococcal vaccines needed after either vaccine 1

For Adults 19-64 Years with Immunocompromising Conditions

• Single dose of PCV21 OR PCV20 1
• Immunocompromising conditions include: chronic renal failure, HIV, malignancy, transplant recipients, asplenia, sickle cell disease 1

For Adults 19-64 Years with Chronic Medical Conditions

• Single dose of PCV21 OR PCV20 1
• Chronic conditions include: diabetes, chronic heart/lung/liver disease, alcoholism, smoking 1

Step 3: Consider Prior Vaccination History

Both PCV20 and PCV21 can be used interchangeably in the following scenarios 1:

• If previously received PPSV23 only: Give PCV21 or PCV20 ≥1 year after last PPSV23 dose 1
• If previously received PCV13 only: Give PCV21 or PCV20 ≥1 year after PCV13 (≥5 years if also received PPSV23) 1
• If completed PCV13 + PPSV23 series: May give PCV21 or PCV20 ≥5 years after last dose via shared decision-making 1

Serotype Coverage Comparison

PCV21 provides broader coverage for emerging serotypes but lacks serotype 4 protection 1:

• During 2018-2022, serotypes in PCV21 caused ~80% of IPD cases in adults with vaccination indications 1
• The 8 unique serotypes in PCV21 accounted for 20-30% of IPD cases 1
• PCV21 addresses racial disparities, as non-PCV13 serotypes disproportionately affect Black adults 1

PCV20 provides serotype 4 coverage, which is critical in specific geographic regions 1:

• Serotype 4 IPD has reemerged after initial decline following PCV7 introduction in children 1
• High serotype 4 prevalence (≥30% of IPD) documented in western U.S. populations 1

Practical Implementation

In most U.S. regions outside the western states, default to PCV21 for its expanded serotype coverage. 1 The 8 additional serotypes address emerging pneumococcal disease patterns and health disparities 1.

In Alaska, Navajo Nation, Colorado, New Mexico, and Oregon, default to PCV20 to ensure serotype 4 protection. 1 This is particularly important for adults <65 years with risk conditions 1.

Once either PCV20 or PCV21 is administered, the pneumococcal vaccination series is complete—no additional doses are needed. 1, 3

Common Pitfalls to Avoid

• Do not assume PCV21 is "better" simply because it has more serotypes—the absence of serotype 4 is clinically significant in high-prevalence areas 1
• Do not administer PPSV23 after PCV20 or PCV21—both vaccines complete the series 1, 3
• Do not co-administer pneumococcal vaccines on the same day 3
• Do not give PCV20 or PCV21 too soon after prior pneumococcal vaccination—observe minimum intervals (≥1 year after PCV13 or PPSV23; ≥5 years if both were given) 1

Safety Profile

Both vaccines demonstrate similar safety profiles 1, 4, 5:

• Local injection site reactions and systemic symptoms comparable to PCV13 4, 5
• No serious vaccine-related adverse events in clinical trials 4, 5
• Contraindicated in severe allergic reaction to vaccine components or diphtheria toxoid 1