Adult Pneumococcal vaccination in the era of PCV20 and PCV21: broader coverage, simpler recommendations

Introduction

Streptococcus pneumoniae remains a major cause of vaccine-preventable morbidity and mortality worldwide. Despite the remarkable success of pediatric pneumococcal conjugate vaccination programs, pneumococcal disease continues to cause substantial burdens of invasive pneumococcal disease (IPD), community-acquired pneumonia, bacteremia, and meningitis among adults, particularly older individuals and those with chronic medical conditions.

The introduction of higher-valent pneumococcal conjugate vaccines (PCVs), specifically PCV20 (Prevnar 20®, Pfizer) and PCV21 (Capvaxive®, Merck), represents one of the most important advances in adult vaccinology in recent years. These vaccines not only expand serotype coverage but also simplify vaccination recommendations, potentially improving vaccine uptake and reducing disease burden among adults at increased risk.

Why Adult Pneumococcal Disease Still Matters

Pneumococcal disease remains a leading cause of hospitalization and death among adults worldwide. Although widespread pediatric vaccination has generated substantial herd protection, the burden of disease persists because of aging populations, increasing prevalence of chronic diseases, and the emergence of non-vaccine serotypes.

Adults at greatest risk include:

• Adults ≥65 years
• Patients with chronic obstructive pulmonary disease (COPD)
• Patients with diabetes mellitus
• Chronic heart disease
• Chronic kidney disease
• Chronic liver disease
• Smokers
• Individuals with immuno-compromising conditions.

Invasive pneumococcal disease continues to be associated with significant mortality, particularly among older adults and immunocompromised individuals.

The Evolution of Adult Pneumococcal Vaccination

For many years, adult vaccination strategies relied on combinations of pneumococcal conjugate vaccines and the 23-valent pneumococcal polysaccharide vaccine (PPSV23). While effective, these schedules were often complex and difficult to implement.

The arrival of PCV20 and PCV21 has simplified adult pneumococcal vaccination by providing broader serotype coverage within a single conjugate vaccine formulation.

PCV20 (Prevnar 20®, Pfizer)

PCV20 contains the 13 serotypes included in PCV13 plus seven additional serotypes associated with substantial residual disease burden:

1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F.

PCV21 (Capvaxive®, Merck)

PCV21 contains:

3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B.[11]

Unlike previous pneumococcal conjugate vaccines, PCV21 was specifically developed using contemporary adult IPD epidemiology as the basis for serotype selection.

Adult-Specific Serotypes: A New Concept in Pneumococcal Prevention

One of the most important recent discoveries in pneumococcal epidemiology is that the serotypes currently causing disease in adults increasingly differ from those affecting children.

Historically, adult pneumococcal vaccination strategies were largely extensions of pediatric vaccine programs. However, successful childhood vaccination has dramatically reduced circulation of several traditional vaccine serotypes, resulting in a shift toward serotypes that disproportionately affect adults.

This observation led to the development of PCV21, which specifically targets serotypes responsible for a substantial proportion of contemporary adult invasive disease, including 15A, 16F, 20, 23A, 23B, 24F, 31, and 35B, several of which are relatively uncommon in pediatric populations.

This represents an important conceptual shift in vaccinology, however, head to head studies comparing the efficacy and/or effectiveness of PCV21 vs PCV20 have not been done, and both vaccines are equally recommended.

Who Should Receive Pneumococcal Vaccination?

Adults ≥65 Years

All adults aged 65 years and older should receive pneumococcal vaccination regardless of underlying health conditions.

This recommendation reflects the substantial burden of pneumococcal disease in older adults and the increased risk of hospitalization, complications, and death.

Adults 19–64 Years with Chronic Medical Conditions

Vaccination is strongly recommended for adults with:

• COPD
• Diabetes mellitus
• Chronic cardiovascular disease
• Chronic kidney disease
• Chronic liver disease
• Alcoholism
• Cigarette smoking.

Immunocompromised Adults

Immunocompromised individuals remain among the highest-risk groups for IPD and severe pneumococcal disease.

These include patients with:

• HIV infection
• Hematologic malignancies
• Solid tumors receiving chemotherapy
• Organ transplantation
• Primary immunodeficiencies
• Immunosuppressive therapies

Vaccination should be prioritized in these populations whenever possible.

Special Considerations for COPD

Among chronic medical conditions, COPD deserves particular attention.

Respiratory infections are major triggers of COPD exacerbations and contribute substantially to hospitalization, healthcare utilization, and mortality.

Pneumococcal vaccination is therefore considered a key preventive strategy in COPD management. Reducing vaccine-type pneumococcal infections may decrease severe respiratory complications and improve long-term outcomes.

Special Considerations for Diabetes

Diabetes mellitus is associated with impaired immune function and increased susceptibility to bacterial infections.

Adults with diabetes experience higher rates of pneumococcal pneumonia, invasive disease, hospitalization, and mortality than non-diabetic individuals.

As the global prevalence of diabetes continues to rise, pneumococcal vaccination should be considered a routine component of comprehensive diabetes care.

Simplifying Recommendations

Perhaps the greatest advantage of PCV20 and PCV21 is the simplification of adult vaccination recommendations.

Historically, multiple sequential schedules involving PCV13, PCV15, and PPSV23 created confusion among providers and patients. Higher-valent conjugate vaccines now allow a simpler approach:

Most adults who require pneumococcal vaccination can receive a single higher-valent conjugate vaccine according to current local recommendations.

Simplified schedules are expected to improve:

• Healthcare provider adherence
• Patient acceptance
• Vaccine coverage rates
• Public health impact

Table 1. Comparison of Current Adult Pneumococcal Conjugate Vaccines

Table 2. Adults at Increased Risk for Pneumococcal Disease

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