What are the differences between Prevnar 20 (20‑valent pneumococcal conjugate vaccine) and other pneumococcal vaccines such as PCV13 and Pneumovax 23?

Key Differences Between Prevnar 20 and Capvaxive (PCV21)

Capvaxive (PCV21) contains 8 unique serotypes not found in any other pneumococcal vaccine but critically lacks serotype 4, which is included in Prevnar 20, making vaccine selection dependent on local epidemiology—particularly in western U.S. regions where serotype 4 causes ≥30% of invasive pneumococcal disease. 1

Serotype Coverage Comparison

Prevnar 20 (PCV20)

• Contains 20 serotypes: 1,3,4,5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F 1, 2
• Includes all 13 serotypes from PCV13 plus 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) 3, 4
• Each 0.5 mL dose contains approximately 2.2 μg of each serotype (except 4.4 μg of 6B), conjugated to 51 μg CRM197 carrier protein 2

Capvaxive (PCV21)

• Contains 21 serotypes with 8 unique additions: Includes serotypes 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B that are not in PCV20, PCV15, or PPSV23 1
• Critical omission: Does NOT contain serotype 4, which is present in Prevnar 20 1
• Shares 13 common serotypes with Prevnar 20 1

Geographic and Clinical Considerations for Vaccine Selection

When Prevnar 20 is Preferred

In western U.S. regions (Alaska, Colorado, Navajo Nation, New Mexico, Oregon), Prevnar 20 should be selected over Capvaxive due to high prevalence of serotype 4 invasive pneumococcal disease (≥30% of cases). 1

• Serotype 4 IPD is particularly prevalent in specific populations including adults with alcoholism, chronic lung disease, cigarette smoking, homelessness, and injection drug use 1
• For patients in midwestern, eastern, and southern U.S. regions without significant serotype 4 circulation, either vaccine is appropriate 1

When Capvaxive May Be Preferred

• Capvaxive provides coverage against 8 serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31, 35B) not available in any other licensed pneumococcal vaccine 1
• May be selected in regions without high serotype 4 prevalence to provide broader coverage against emerging serotypes 1

Immunologic Mechanism (Identical Between Both Vaccines)

Both Prevnar 20 and Capvaxive are pneumococcal conjugate vaccines that share the same immunologic advantages over polysaccharide vaccines:

• Induce T-cell dependent immune responses with memory B-cell formation, providing stronger and longer-lasting protection 5, 6
• Polysaccharides are conjugated to carrier protein (CRM197 for Prevnar 20), which activates T-helper cells and creates immunologic memory 5, 2
• Reduce nasopharyngeal carriage of pneumococci, creating herd immunity effects 5
• Effective even in immunocompromised patients and infants due to T-cell dependent mechanism 5

Current ACIP Recommendations (2024)

ACIP now recommends PCV21 (Capvaxive) as an option alongside PCV20 or PCV15 followed by PPSV23 for all adults ≥65 years and adults 19-64 years with risk conditions who have not received PCV or whose vaccination history is unknown. 1

Standard Vaccination Options

• PCV20 alone (single dose) 1
• PCV15 followed by PPSV23 (≥1 year later for most adults, minimum 8 weeks for immunocompromised) 1
• PCV21 alone (single dose, newly added option) 1

For Previously Vaccinated Adults

• Adults who received PCV13 only can receive either PCV20 or PCV21 to expand coverage 1
• Adults who received both PCV13 and PPSV23 but not final PPSV23 dose at age ≥65 can complete series with PCV20 ≥5 years after last dose 1

Safety and Tolerability

Prevnar 20

• Well tolerated with safety profile similar to PCV13 7, 4
• Most common adverse reactions: injection site pain, fatigue, and myalgia 2
• Serious adverse events within 6 months: 2.5% (comparable to 2.4% for PCV13) 1
• No deaths considered vaccine-related in clinical trials 1

Capvaxive

• Safety data from FDA licensure in June 2024 demonstrated comparable tolerability to other PCVs 1
• Postlicensure monitoring ongoing 1

Critical Clinical Pitfalls to Avoid

• Never use PPSV23 alone in children under 2 years—it provides no protection in this age group due to inability to mount T-independent immune responses 5
• Always administer PCV before PPSV23 when both are indicated to optimize immune response 5
• In western U.S. regions with high serotype 4 prevalence, do not select Capvaxive for patients at risk for serotype 4 disease 1
• Prior PPSV23 vaccination may reduce responsiveness to subsequent pneumococcal vaccination 5