Should Pneumococcal Conjugate Vaccine 20 (PCV-20) be administered after Pneumococcal Conjugate Vaccine 23 (PCV-23)?

Administration of PCV-20 After PCV-23 Vaccination

Adults who have received PPSV23 (PCV-23) should receive a single dose of PCV-20 ≥1 year after the last PPSV23 dose, with no need for additional pneumococcal vaccines afterward. 1

Rationale and Evidence Base

The Advisory Committee on Immunization Practices (ACIP) provides clear guidance on this scenario based on the immunologic advantages of pneumococcal conjugate vaccines (PCVs) compared to polysaccharide vaccines (PPSV23):

• PCV-20 contains additional serotypes not contained in earlier PCVs (like PCV13)
• PCVs generally provide superior immunologic response compared to polysaccharide vaccines
• PPSV23 has limited duration of protection 1

Timing Considerations

• The recommended interval between prior PPSV23 and subsequent PCV-20 administration is ≥1 year
• When PCV-20 is used in adults who previously received PPSV23, no additional pneumococcal vaccine doses are needed 1

Clinical Evidence Supporting This Approach

A Phase 3 clinical trial specifically evaluated PCV-20 in adults ≥65 years with different prior pneumococcal vaccination histories, including those who had previously received PPSV23. The study demonstrated:

• PCV-20 was well-tolerated in adults with prior PPSV23 vaccination
• Robust immune responses, including opsonophagocytic antibody responses, were observed to all 20 vaccine serotypes regardless of prior vaccination history
• Safety profiles were comparable between PCV-20 and control groups 2

Special Populations

Immunocompromised Patients

For patients with immunocompromising conditions who have received PPSV23, the same recommendation applies - they should receive PCV-20 ≥1 year after their last PPSV23 dose. This approach provides broader serotype coverage with the immunologic advantages of a conjugate vaccine 1.

Hematopoietic Stem Cell Transplant (HSCT) Recipients

HSCT recipients represent a special case:

• Current US recommendations suggest revaccinating all HSCT recipients with PCV-20 starting at 4-6 months post-transplant
• The schedule consists of three doses at 1-month intervals, followed by a fourth dose 6 months later
• Patients who started revaccination with PCV-15 can complete subsequent doses with PCV-20 1

Potential Concerns and Pitfalls

Hyporesponsiveness Concerns

Some clinicians may worry about potential hyporesponsiveness when administering conjugate vaccines after polysaccharide vaccines. However, published data suggest immune responses following sequential vaccination are robust without evidence of clinically significant hyporesponsiveness 3.

Drug Interactions

The FDA label for PCV-20 notes that receipt of PPSV23 1-5 years prior to PCV-20 resulted in diminished opsonophagocytic activity geometric mean titers compared to other vaccination sequences 4. However, this finding has not altered the ACIP recommendations to administer PCV-20 after PPSV23, as the clinical significance appears limited.

Summary of Approach

1. Identify patients who have previously received PPSV23
2. Ensure at least 1 year has passed since the last PPSV23 dose
3. Administer a single dose of PCV-20
4. No further pneumococcal vaccines are needed after PCV-20 administration

This approach aligns with the goal of providing optimal protection against pneumococcal disease by leveraging the expanded serotype coverage and immunologic advantages of conjugate vaccines.