Should PCV21 (Pneumococcal Conjugate Vaccine 21) or PCV20 (Pneumococcal Conjugate Vaccine 20) be used for pneumococcal disease prevention in [LOCATION]?

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Last updated: December 16, 2025View editorial policy

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PCV20 vs PCV21 Selection Based on Geographic Location

In most U.S. regions (Midwest, East, South), PCV20 is the preferred choice over PCV21 because it provides broader serotype coverage including serotype 4, which PCV21 lacks. 1

Geographic-Based Decision Algorithm

Choose PCV20 in these locations:

  • Midwestern, Eastern, and Southern United States - These regions have not detected significant percentages of serotype 4 invasive pneumococcal disease (IPD), and PCV20 provides broader coverage against locally circulating strains compared to PCV21 1

  • Any location where serotype 4 IPD is <30% - PCV20 alone or PCV15 + PPSV23 are expected to provide superior protection 1

Choose PCV21 in these specific high-risk locations:

  • Alaska - High percentages (≥30%) of IPD caused by serotype 4 have been documented 1

  • Colorado - Significant serotype 4 burden identified 1

  • Navajo Nation - Particularly high serotype 4 prevalence 1

  • New Mexico - Elevated serotype 4 IPD rates 1

  • Oregon - High serotype 4 disease burden 1

  • Other Western U.S. states without surveillance data - Consider PCV21 if local epidemiology suggests high serotype 4 burden, though data are currently unknown 1

Key Serotype Coverage Differences

Critical caveat: PCV21 contains eight pneumococcal serotypes not included in PCV15, PCV20, or PPSV23, but it lacks serotype 4 which is present in PCV20 1

  • In non-Western regions, serotype 4 IPD typically occurs in adults <65 years with specific risk factors: alcoholism, chronic lung disease, cigarette smoking, homelessness, and injection drug use 1

  • These at-risk individuals usually have not received any pneumococcal conjugate vaccine containing serotype 4, making PCV20 particularly valuable 1

General Recommendations for All Locations

Both PCV20 and PCV21 are ACIP-approved options for adults ≥19 years who are recommended to receive pneumococcal conjugate vaccine 1, 2

Standard dosing:

  • Single dose of PCV20 or PCV21 completes the vaccination series with no additional doses needed 2, 3
  • If PCV15 is used instead, follow with PPSV23 at ≥1 year (immunocompetent) or ≥8 weeks (immunocompromised) 2, 3

Clinical Pitfalls to Avoid

  • Do not assume PCV21 is automatically superior because it has more serotypes - the absence of serotype 4 is clinically significant in most U.S. regions 1

  • Do not use PCV21 as default in Western states without confirming local serotype 4 epidemiology - only specific areas have documented high serotype 4 burden 1

  • Reassess vaccination needs at age 65 for adults who received pneumococcal vaccines before this age 1

  • Never administer PCV and PPSV23 on the same day - maintain appropriate intervals 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Pneumococcal Vaccine Recommendations for Adults

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Pneumococcal Vaccination for Patients with Pulmonary Tuberculosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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