MedPath

Pneumococcal 13-valent conjugate vaccine (Pfizer) Advanced Drug Monograph

Published:Oct 1, 2025

A Comprehensive Clinical and Immunological Review of the Pneumococcal 13-valent Conjugate Vaccine (PCV13, Pfizer)

Section 1: Vaccine Profile and Immunological Mechanism

The Pneumococcal 13-valent Conjugate Vaccine (PCV13), developed and manufactured by Pfizer under the brand name Prevnar 13®, represents a significant advancement in the prevention of diseases caused by Streptococcus pneumoniae. Its design, based on sophisticated conjugate technology, allows it to elicit a robust and durable immune response across a wide range of age groups, including those with immature or aging immune systems. This section details the vaccine's composition and the immunological principles that underpin its high degree of efficacy.

1.1 Composition and Formulation

Prevnar 13® is a sterile suspension for intramuscular injection. Its active components are purified capsular polysaccharides from 13 distinct serotypes of Streptococcus pneumoniae, which were strategically selected based on their global prevalence, association with severe disease, and potential for antibiotic resistance.[1]

Antigenic Components: The 13 serotypes included in the vaccine are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.[1] These include the seven serotypes from the original 7-valent vaccine (PCV7) plus six additional serotypes (1, 3, 5, 6A, 7F, and 19A) that were responsible for a growing proportion of invasive pneumococcal disease (IPD) following the widespread use of PCV7.[4]

Formulation Details: Each 0.5 mL single-dose pre-filled syringe is precisely formulated to deliver a consistent antigenic load. The dose contains approximately 2.2 µg of saccharide for each of the 12 serotypes and a doubled concentration of 4.4 µg for serotype 6B.[1] This differential dosing for serotype 6B is a feature carried over from PCV7, designed to ensure a robust immune response against this historically prevalent serotype. All 13 polysaccharide saccharides are individually conjugated to a carrier protein, CRM197, with a total protein content of approximately 34 µg per dose.[1]

The formulation also includes several key excipients:

  • Adjuvant: 125 µg of aluminum, in the form of aluminum phosphate, is included to enhance the magnitude and duration of the immune response.[1]
  • Stabilizer: 100 µg of polysorbate 80 prevents the vaccine components from adhering to the container and maintains the suspension's integrity.[1]
  • Buffer: 295 µg of succinate buffer is used to maintain a stable pH.[1]

Manufacturing Process: The production of PCV13 is a multi-step process. Each pneumococcal serotype is grown in a soy peptone broth, and its unique capsular polysaccharide is harvested and purified using methods such as centrifugation, precipitation, and chromatography.[1] The purified polysaccharides are then chemically activated to form saccharides, which are subsequently covalently linked to the CRM197 carrier protein through a process called reductive amination. The resulting individual glycoconjugates are purified and analyzed to ensure proper saccharide-to-protein ratios before being compounded into the final vaccine formulation.[1] The carrier protein, CRM197, is a non-toxic variant of the diphtheria toxin, ensuring safety while providing the necessary protein component to stimulate a comprehensive immune response.[1]

1.2 Mechanism of Action: Eliciting T-Cell Dependent Immunity

The fundamental innovation of PCV13 lies in its conjugate technology, which transforms the immune response from a T-cell-independent process, characteristic of polysaccharide-only vaccines, into a highly effective T-cell dependent response.[7] This distinction is the primary reason for its superior immunogenicity in infants and its ability to induce long-lasting protection.

The Conjugate Principle and Immunological Cascade: Polysaccharide antigens, when presented alone, primarily stimulate B-lymphocytes directly without the involvement of T-helper cells. This T-cell-independent pathway is poorly developed in infants under two years of age and generates a relatively weak antibody response with little to no immunological memory, rendering polysaccharide vaccines like the 23-valent pneumococcal polysaccharide vaccine (PPSV23) ineffective in this critical age group.[6]

By covalently linking the pneumococcal polysaccharides to the CRM197 carrier protein, PCV13 effectively engages the T-cell arm of the adaptive immune system. B-cells that recognize the polysaccharide component of the vaccine internalize the entire glycoconjugate. They then process the CRM197 protein and present its peptides on their surface via MHC class II molecules. These peptide-MHC complexes are recognized by protein carrier-specific T-helper cells, which in turn provide essential co-stimulatory signals to the B-cells.[7] This T-cell "help" is crucial for driving the full maturation of the B-cell response, including affinity maturation (production of higher-quality antibodies), immunoglobulin class switching, and the generation of a robust population of long-lived plasma cells and memory B-cells.[11] This creation of immune memory is a hallmark of conjugate vaccines and is essential for providing durable protection against future infection.

This sophisticated molecular engineering is the direct cause of PCV13's profound success in infants. It effectively circumvents a key limitation of the infant immune system by providing the necessary protein component for T-cell recognition, a landmark achievement in vaccinology. Furthermore, the proven success of this CRM197-conjugation platform in PCV7 and PCV13 established a trusted technological and regulatory pathway. This foundation enabled the subsequent development and approval of higher-valency vaccines, such as PCV15 and Pfizer's own PCV20 (Prevnar 20®), which are explicitly described as being "built on the efficacy and real-world effectiveness of Prevnar 13®".[2] The focus of innovation shifted from creating a new mechanism to expanding serotype coverage on a validated, highly effective platform.

Correlates of Protection: The ultimate goal of the immune response is the production of functional antibodies capable of eliminating the bacteria. Protection against pneumococcal disease is believed to be mediated by antibodies that facilitate opsonophagocytosis—the process of "tagging" the encapsulated bacteria for engulfment and destruction by phagocytic immune cells.[7] This functional activity is measured

in vitro using an Opsonophagocytic Activity (OPA) antibody assay.

  • In Infants: In clinical trials with infants, a serum anti-capsular polysaccharide IgG antibody concentration of  µg/mL, as measured by a standardized ELISA one month after the third dose, was established as a reference concentration used to estimate the vaccine's effectiveness against IPD on a population basis.[7] This surrogate marker correlates well with functional OPA titers in this age group.
  • In Adults: A specific protective IgG antibody level to predict protection against IPD or non-bacteremic pneumonia has not been defined for adults. Therefore, the immunogenicity of PCV13 in adults was established in non-inferiority trials by demonstrating that the functional OPA antibody responses it generated were non-inferior, and for some serotypes superior, to those induced by the established PPSV23 vaccine.[7]

Section 2: Clinical Development and Efficacy in Adult Populations

The approval and subsequent widespread recommendation of PCV13 for adults were supported by a comprehensive clinical development program, culminating in one of the largest vaccine efficacy trials ever conducted. This body of evidence established not only the vaccine's robust immunogenicity but also its definitive clinical benefit in preventing pneumococcal pneumonia and invasive disease in older adults.

2.1 The CAPiTA Trial: A Landmark Study in Older Adults

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) stands as the pivotal study confirming the clinical efficacy of PCV13 in an older adult population.

Study Design and Significance: CAPiTA was a large-scale, prospective, double-blind, randomized, placebo-controlled trial conducted in the Netherlands. It enrolled approximately 85,000 community-dwelling adults aged 65 years and older.[13] The trial's immense scale and rigorous design were necessary to definitively assess the vaccine's efficacy against clinical endpoints, particularly non-bacteremic pneumonia. The study was undertaken as a post-marketing commitment to regulatory agencies, as PCV13 had received its initial adult indication under an accelerated approval pathway based on immunogenicity data alone.[13]

Primary and Secondary Endpoints: The trial was designed to evaluate three key clinical outcomes and successfully met all of its objectives.[13]

  • Primary Objective: To demonstrate efficacy against a first episode of vaccine-type community-acquired pneumonia (VT-CAP).
  • Secondary Objectives: To demonstrate efficacy against a first episode of non-bacteremic/non-invasive VT-CAP and a first episode of vaccine-type IPD.

Efficacy Results: The per-protocol analysis demonstrated statistically significant and clinically meaningful reductions in pneumococcal disease among those who received PCV13 compared to placebo. The results provided clear evidence of the vaccine's protective effect.[12]

The most impactful finding from CAPiTA was the robust efficacy against non-bacteremic pneumonia.[14] Prior to this trial, the public health value of adult pneumococcal vaccination was primarily framed around preventing the relatively rare but severe outcome of IPD. However, non-bacteremic pneumonia constitutes the vast majority of the pneumococcal disease burden in adults.[23] By proving efficacy against this endpoint—a notoriously difficult feat in vaccine trials—CAPiTA fundamentally expanded the demonstrated clinical benefit of PCV13. This groundbreaking evidence provided the solid foundation for the 2014 Advisory Committee on Immunization Practices (ACIP) recommendation for its routine use in all adults aged 65 and older, shifting the paradigm for adult pneumococcal vaccination from a niche intervention for preventing sepsis to a broad public health tool for preventing common, burdensome pneumonia hospitalizations.[22]

Table 2: Summary of Efficacy Results from the CAPiTA Trial (Per-Protocol Analysis)

Clinical EndpointPrevnar 13 Group (Events)Placebo Group (Events)Vaccine Efficacy (VE)95.2% Confidence Interval (CI)P-Value
First Episode of Vaccine-Type CAP (Primary)499045.6%21.8% to 62.5%0.0006
First Episode of Non-Bacteremic/Non-Invasive VT-CAP336045.0%14.2% to 65.3%0.0067
First Episode of Vaccine-Type IPD72875.0%41.1% to 90.9%0.0005

Durability of Protection: A crucial finding from post-hoc analysis was the durability of the vaccine's protection. Efficacy was observed to begin shortly after vaccination and persisted throughout the trial's mean follow-up period of approximately four years, with no statistical evidence of waning protection over time.[14]

2.2 Immunogenicity and Safety in Adults (18-64 years)

Regulatory approval for PCV13 use in adults younger than 65 years was granted based on immunogenicity bridging studies. These trials were designed to demonstrate that the immune responses in younger adults were comparable to those in the older adult population in which clinical efficacy was established.

  • Bridging Studies: Clinical trials in adults aged 18 to 49 and 50 to 64 demonstrated that PCV13 elicited an immune response, as measured by OPA antibody titers, that was non-inferior to the response seen in the 60 to 64-year-old cohort.[25] This immunological evidence allowed for the extrapolation of efficacy data to these younger age groups.
  • Superior Immunogenicity vs. PPSV23: A consistent finding across multiple randomized clinical trials in adults was the superior immunogenicity of PCV13 compared to PPSV23 for the majority of the 12 serotypes shared between the two vaccines.[12] PCV13 elicited significantly higher OPA titers, indicating a more robust functional antibody response, which is believed to be a key mechanism of protection.

2.3 Real-World Effectiveness in Adults

Post-licensure observational studies are essential for confirming that a vaccine's efficacy, as measured in a controlled clinical trial, translates to effectiveness in routine clinical practice, particularly among populations with comorbidities who may have been excluded from pivotal trials.

  • Validation in High-Risk Populations: The CAPiTA trial largely excluded individuals with immunocompromising conditions that place them at high risk for pneumococcal disease.[22] A subsequent U.S.-based, test-negative design case-control study provided critical real-world evidence. This study, which included adults aged 65 and older with a range of underlying medical conditions, found a vaccine effectiveness of 73% (95% CI: 12.8%–91.5%) in preventing hospitalization from VT-CAP.[22] This result confirmed the vaccine's substantial benefit in a more representative, co-morbid population.
  • The observation that real-world effectiveness against hospitalization (73%) was substantially higher than the clinical trial efficacy against a first episode of VT-CAP (45.6%) is noteworthy.[22] While methodological differences between an observational study and a randomized controlled trial prevent direct comparison, this finding suggests that under the complex conditions of a real-world immunization program, the vaccine's protective effect against severe outcomes like hospitalization may be even more pronounced than demonstrated in the controlled trial setting. This could be due to the prevention of subsequent or more severe episodes of pneumonia, effects on disease that did not meet the strict trial endpoint definition, or other unmeasured factors, strongly reinforcing the vaccine's public health value.
  • Effectiveness in Specific Conditions: Evidence has also emerged for specific high-risk groups. An observational study in individuals with reduced kidney function, a population known to have a blunted immune response to vaccination, demonstrated that PCV13 had a vaccine effectiveness of 39% against pneumococcal hospitalization and bacteremia. In contrast, PPSV23 showed no clear evidence of effectiveness in this same high-risk group, highlighting the clinical advantage of the conjugate vaccine technology.[30]

Section 3: Pediatric Application: Efficacy, Effectiveness, and Safety

The introduction of PCV13 into pediatric immunization schedules marked a pivotal moment in the global fight against pneumococcal disease. Building on the success of its predecessor, PCV7, the expanded coverage of PCV13 led to dramatic and sustained reductions in the incidence of pneumonia, meningitis, and other severe infections in children.

3.1 Foundational Efficacy and Immunogenicity in Infants

PCV13 was licensed by the U.S. Food and Drug Administration (FDA) for use in infants and young children on February 24, 2010, designed to replace the 7-valent vaccine (PCV7) in the routine immunization schedule.[4]

  • Regulatory Pathway: The approval of PCV13 was based on a series of 13 Phase III clinical trials involving over 7,000 infants and young children.[4] The regulatory strategy relied on demonstrating immunological non-inferiority to the already licensed and highly effective PCV7. The studies confirmed that the immune responses to the seven serotypes shared with PCV7 were comparable, and that PCV13 generated a robust and presumably protective immune response to the six new serotypes (1, 3, 5, 6A, 7F, and 19A) for which there was a significant disease burden.[4]
  • Public Health Impact: The implementation of pediatric pneumococcal conjugate vaccine programs has been a resounding public health success. Over a 20-year period in the United States, the use of PCV7 and subsequently PCV13 is estimated to have averted over 282,000 cases of IPD, including approximately 16,000 cases of meningitis and 172,000 cases of bacteremia, among children younger than 5 years.[10] The impact extended to less severe but highly common illnesses as well, preventing an estimated 97 million healthcare visits for acute otitis media.[10]

3.2 Post-Licensure Effectiveness in Children

Because PCV13 was licensed for pediatric use based on immunogenicity data rather than a large-scale efficacy trial, post-licensure observational studies have been critical for quantifying its real-world effectiveness.

  • Overall Effectiveness: A comprehensive U.S. case-control study conducted from 2010 to 2019 provided robust evidence of the vaccine's performance. Among children under 5 years of age who had received a complete primary series (defined as  doses), the vaccine effectiveness (VE) was 90.2% (95% CI: 75.4%–96.1%) against IPD caused by the 13 serotypes contained in the vaccine.[31]
  • Serotype-Specific Effectiveness: The same study offered crucial insights into performance against specific serotypes. VE was high against serotype 19A (86.8%) and serotype 19F (93.8%), two major causes of disease.[31] However, a key limitation of the vaccine was identified in its performance against serotype 3. The calculated VE against serotype 3 IPD was 50.2%, but this finding was not statistically significant (95% CI: 28.4%–80.5%), suggesting suboptimal protection.[31] This finding is consistent with immunogenicity data from infant trials, which showed that the immune response to serotype 3 did not increase following the booster dose compared to levels seen after the primary infant series.[5] This recurring theme of suboptimal performance against the highly virulent serotype 3 represented a key unmet medical need. This "serotype 3 problem" was a direct driver for the development of next-generation vaccines, such as PCV15 and PCV20, which were specifically engineered to elicit a superior immune response to this challenging serotype. Indeed, subsequent clinical trial data demonstrated that PCV15 elicited a statistically significantly higher immune response to serotype 3 than PCV13 did, directly addressing this known limitation.[33]
  • Effectiveness Against Other Conditions: Beyond preventing invasive disease, widespread PCV use has been shown to significantly reduce the burden of other common childhood illnesses. Studies have demonstrated an associated 20% reduction in episodes of chest X-ray confirmed pneumonia, a 7% reduction in acute otitis media, and a 20% reduction in the placement of tympanostomy tubes for recurrent ear infections.[18]

3.3 Pediatric Safety Profile

The safety profile of PCV13 in infants and children is well-established and consistent with that of other routinely administered pediatric vaccines.

  • Common Adverse Events: Data from extensive clinical trials show that the most frequently reported solicited adverse reactions are generally mild and self-limiting. In infants and toddlers, these include irritability (reported in >70% of recipients), injection site tenderness (>50%), decreased appetite (>40%), alterations in sleep patterns (either decreased or increased sleep, >40%), and fever (>20%).[3]
  • Special Populations (Premature Infants): A specific warning is included in the prescribing information regarding the potential risk of apnea (a temporary cessation of breathing) following intramuscular vaccination in some infants born prematurely.[1] The decision to administer PCV13 to a premature infant requires careful consideration of the individual's medical status, balancing the potential risks against the high benefit of vaccination in this vulnerable group. In practice, this often involves respiratory monitoring for 48 to 72 hours after vaccination for infants with a history of respiratory immaturity.[32]

Section 4: Immunization Recommendations and Strategic Use

The clinical recommendations for PCV13 have evolved significantly since its introduction, reflecting its initial role as a best-in-class vaccine and its subsequent transition in an era of even broader-coverage conjugate vaccines. This evolution has been driven by the vaccine's own success in altering the epidemiology of pneumococcal disease.

4.1 U.S. CDC Immunization Schedules

The U.S. Centers for Disease Control and Prevention (CDC) provides detailed recommendations for pneumococcal vaccination across the lifespan.

  • Pediatric Routine Vaccination: The original routine schedule for PCV13 consisted of a four-dose series administered at ages 2, 4, 6, and 12-15 months.[4] With the licensure of higher-valency vaccines, the current CDC recommendations now list PCV15 or PCV20 as the preferred options for the routine infant series. PCV13 remains an acceptable alternative if the newer vaccines are unavailable, prioritizing the act of vaccination over the specific product to avoid missed opportunities.[19] Comprehensive catch-up schedules are available for children who are unvaccinated or fall behind the recommended schedule.[40]
  • Adult Vaccination ( years): In 2014, based on the strength of the CAPiTA trial results, the CDC's ACIP made a landmark recommendation for the routine use of PCV13 in series with PPSV23 for all adults aged 65 years and older.[24] This recommendation has since been updated following the introduction of PCV15 and PCV20 in 2021. For adults in this age group who are pneumococcal vaccine-naïve, the current recommendation is to administer a single dose of PCV20, or a dose of PCV15 followed by a dose of PPSV23.[43] For individuals who have already received PCV13, the decision to administer a dose of a higher-valency vaccine is now based on shared clinical decision-making between the patient and provider.[38]
  • High-Risk and Immunocompromised Individuals: PCV13 has been a cornerstone of vaccination for individuals aged 2 through 64 years with conditions that increase their risk of pneumococcal disease, such as functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, cochlear implants, and a range of immunocompromising conditions including HIV infection, chronic renal failure, and malignancy.[35] The recommended strategy for these patients has typically involved administering PCV13 first to prime the immune system and establish immunologic memory, followed at a later interval (typically at least 8 weeks) by one or more doses of PPSV23 to provide protection against a broader range of serotypes.[38] Current guidelines are now transitioning these high-risk patients to receive PCV15 or PCV20 as their initial conjugate vaccine dose.[45]

4.2 The Evolving Role of PCV13 in the Era of Higher-Valency Vaccines

The shifting recommendations for PCV13, particularly in the adult population, provide a sophisticated case study in modern public health strategy, demonstrating a dynamic interplay between direct vaccine efficacy, indirect population effects, and the introduction of new technology.

  • Impact of Herd Immunity: The most significant factor influencing the evolution of PCV13's role has been its own success. The widespread and routine use of PCV13 in the pediatric national immunization program led to a profound reduction in the nasopharyngeal carriage and transmission of the 13 vaccine-type serotypes within the community. This created a powerful indirect protective effect, known as "herd immunity," which dramatically reduced the incidence of PCV13-type disease even among unvaccinated adults.[20]
  • Rationale for Shifting Recommendations: This robust herd immunity effect was the primary rationale for the ACIP's 2019 decision to change its recommendation for routine PCV13 use in all immunocompetent adults  years from "routine for all" to one based on "shared clinical decision-making".[20] The population-level benefit of vaccinating every healthy older adult with PCV13 was diminishing because the targeted serotypes were already being suppressed by the pediatric program. This epidemiological shift created a strategic opening for a new approach focused on providing broader protection against the remaining non-PCV13 serotypes that were now causing the majority of adult disease. This role is now filled by the higher-valency PCV15 and PCV20 vaccines.
  • Current Positioning: In the current landscape, PCV13 is largely considered a legacy vaccine in countries like the United States where higher-valency options are available. While still licensed and highly effective against its target serotypes, it is no longer the preferred conjugate vaccine for routine use in any age group. Its primary role is as a permissible substitute when PCV15 or PCV20 are unavailable, ensuring that vaccination is not deferred.[19]

Table 1: Comparative Analysis of Pneumococcal Vaccines

FeaturePCV13 (Prevnar 13®)PCV15 (Vaxneuvance®)PCV20 (Prevnar 20®)PPSV23 (Pneumovax 23®)
ManufacturerPfizerMerckPfizerMerck
Vaccine TechnologyConjugateConjugateConjugatePolysaccharide
Serotypes Covered13 Serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F15 Serotypes: All 13 from PCV13 plus 22F, 33F20 Serotypes: All 13 from PCV13 plus 8, 10A, 11A, 12F, 15B, 22F, 33F23 Serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F

Section 5: Comprehensive Safety Monograph and Regulatory History

A thorough understanding of a vaccine's safety profile and regulatory journey is essential for clinical practice. Prevnar 13® has been administered to millions of individuals worldwide, and its safety has been extensively studied in clinical trials and monitored through post-marketing surveillance systems.

5.1 Contraindications, Warnings, and Precautions

The administration of PCV13 is guided by specific contraindications and precautions to ensure patient safety.

  • Absolute Contraindication: The vaccine is strictly contraindicated for any individual with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13® or to any diphtheria toxoid-containing vaccine.[1]
  • Warnings and Precautions:
  • Apnea: As with other intramuscular vaccines, apnea has been observed in some infants born prematurely. The decision to administer the vaccine to this population should be based on the individual infant's medical status and the potential benefits and risks, with consideration for respiratory monitoring post-vaccination.[32]
  • Altered Immunocompetence: Individuals with functional or anatomic asplenia, HIV infection, or other immunocompromising conditions (e.g., due to malignancy or immunosuppressive therapy) may have a diminished antibody response to active immunization.[13]
  • Acute Illness: Vaccination should be postponed in individuals suffering from a moderate or severe acute illness with or without fever.[32]

5.2 Adverse Event Profile

The adverse event profile for PCV13 is well-characterized and consistent across different age groups, with most reactions being mild and transient.

  • Local Reactions: The most common adverse events are reactions at the injection site. These include pain or tenderness (reported in >50% of recipients across all age groups), redness (erythema), and swelling. These reactions are typically mild and resolve within a few days.[3]
  • Systemic Reactions: Common systemic reactions vary slightly by age but generally include irritability (especially in infants), fatigue, headache, myalgia (muscle pain), arthralgia (joint pain), decreased appetite, and low-grade fever. These reactions are also typically self-limiting and resolve without intervention.[3]
  • Serious Adverse Events: While rare, serious adverse events have been reported through post-marketing surveillance. These include anaphylactic/anaphylactoid reactions, angioneurotic edema (swelling under the skin), and erythema multiforme.[34] The safety profile observed in the large-scale CAPiTA trial, involving over 42,000 recipients of PCV13, was consistent with that seen in previous studies, and no new or unexpected safety concerns were identified.[13]

Table 3: Summary of Common Solicited Adverse Reactions by Age Group (Frequency >20%)

Adverse ReactionInfants & Toddlers (US Trials)Children 5-17 yearsAdults  years
Irritability>70%>20%N/A
Injection Site Tenderness/Pain>50%>80%>50%
Decreased Appetite>40%>20%>10%
Decreased Sleep>40%>5%N/A
Increased Sleep>40%>20%N/A
Fever ()>20%>5%>5%
Injection Site Redness>20%>30%>10%
Injection Site Swelling>20%>30%>10%
FatigueN/AN/A>30%
HeadacheN/AN/A>20%
Muscle PainN/AN/A>20%

5.3 Global Regulatory Approvals

Prevnar 13® has received widespread approval from major regulatory agencies around the world, reflecting the strength of its clinical data.

  • U.S. Food and Drug Administration (FDA):
  • February 24, 2010: Initial approval for active immunization in children 6 weeks through 5 years of age.[4]
  • December 2011: Indication expanded to include adults aged 50 years and older, granted under an accelerated approval pathway.[16]
  • January 2013: Indication expanded to include children and adolescents aged 6 through 17 years.[56]
  • July 2016: Indication further expanded to include adults aged 18 through 49 years, making it the only pneumococcal vaccine in the U.S. approved across the lifespan at that time.[27]
  • European Medicines Agency (EMA):
  • December 2009: First approved as Prevenar 13 for use in infants and young children.[26]
  • The indication was subsequently expanded to include adults aged 50 and older, and later to all adults aged 18 years and older, making it the first pneumococcal vaccine in the European Union approved to provide protection from infancy through all stages of adulthood.[25]
  • Australia - Therapeutic Goods Administration (TGA):
  • March 2010: Initially registered for use in infants and children.[58]
  • October 2011: Indication extended to adults aged 50 years and older.[58]
  • May 2014: Indication further extended to include adults aged 18 to 49 years.[59]

Conclusion

The Pneumococcal 13-valent Conjugate Vaccine, Prevnar 13®, represents a landmark achievement in vaccine science and public health. Its innovative use of conjugate technology successfully overcame the immunological limitations of earlier polysaccharide vaccines, enabling robust, T-cell dependent, and durable immunity in the most vulnerable populations: infants and older adults. The pivotal CAPiTA trial provided definitive evidence of its efficacy in preventing not only invasive pneumococcal disease but also the far more common outcome of non-bacteremic community-acquired pneumonia in adults, fundamentally reshaping vaccination strategies worldwide.

In the pediatric population, the introduction of PCV13 led to a profound and sustained decline in the incidence of pneumococcal meningitis, bacteremia, and otitis media. The vaccine's success was so significant that the resulting herd immunity dramatically reduced the circulation of vaccine-type serotypes in the community, thereby altering the epidemiology of the disease in unvaccinated adults. This epidemiological shift, a direct consequence of the vaccine's effectiveness, has in turn driven the evolution of public health recommendations, paving the way for newer, higher-valency conjugate vaccines designed to target the remaining serotypes.

While now largely succeeded by PCV15 and PCV20 in routine immunization schedules in some countries, PCV13's legacy is undeniable. It established a new standard of care, demonstrated the immense potential of conjugate vaccine platforms, and created the public health conditions that necessitated the next generation of pneumococcal vaccines. Its well-characterized safety profile and proven effectiveness ensure it remains a critical tool in the global effort to control pneumococcal disease.

Works cited

  1. PREVNAR 13® (pneumococcal 13-valent conjugate vaccine ..., accessed October 1, 2025, https://www.pfizermedical.com/prevnar-13/description
  2. PREVNAR 20® (Pneumococcal 20-valent Conjugate Vaccine) | for HCPs, accessed October 1, 2025, https://prevnar20adult.pfizerpro.com/
  3. full Prescribing Information for Prevnar 13 - Pfizer, accessed October 1, 2025, https://labeling.pfizer.com/showlabeling.aspx?id=501
  4. Pfizer Receives FDA Approval for Prevnar 13™ for the Prevention of Invasive Pneumococcal Disease in Infants and Young Children, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_fda_approval_for_prevnar_13_for_the_prevention_of_invasive_pneumococcal_disease_in_infants_and_young_children
  5. Pneumococcal Polysaccharide Conjugate Vaccine (Adsorbed) IP, 13-valent PREVENAR 13 - Pfizer, accessed October 1, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=15009
  6. Pneumococcal disease | The Australian Immunisation Handbook, accessed October 1, 2025, https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/pneumococcal-disease
  7. PREVNAR 13® (pneumococcal 13-valent conjugate vaccine ..., accessed October 1, 2025, https://www.pfizermedical.com/prevnar-13/clinical-pharmacology
  8. www.pfizermedical.com, accessed October 1, 2025, https://www.pfizermedical.com/prevnar-13/clinical-pharmacology#:~:text=12.1%20Mechanism%20of%20Action,of%20the%20B%2Dcell%20response.
  9. What is the approval history and clinical development pathway of Prevnar Family?, accessed October 1, 2025, https://synapse.patsnap.com/article/what-is-the-approval-history-and-clinical-development-pathway-of-prevnar-family
  10. Twenty-Year Public Health Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines in US Children - PMC, accessed October 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8153862/
  11. Mechanism of Action | Prevenar 13 - PfizerPro India, accessed October 1, 2025, https://www.pfizerpro.in/medicine/prevenar13-adult/about/mechanism-of-action
  12. Efficacy and Safety of the Pneumococcal Conjugate-13 Valent Vaccine in Adults - PMC, accessed October 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6457056/
  13. Pfizer Announces Positive Top-Line Results Of Landmark ..., accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_positive_top_line_results_of_landmark_community_acquired_pneumonia_immunization_trial_in_adults_capita_evaluating_efficacy_of_prevenar_13
  14. Pfizer Presents Detailed Results From Landmark Community-Acquired Pneumonia Immunization Trial In Adults (CAPiTA) Evaluating Efficacy Of Prevenar 13, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_presents_detailed_results_from_landmark_community_acquired_pneumonia_immunization_trial_in_adults_capita_evaluating_efficacy_of_prevenar_13
  15. CAPiTa Clinical Study - PREVNAR 20® (Pneumococcal 20-valent Conjugate Vaccine), accessed October 1, 2025, https://prevnar20adult.pfizerpro.com/clinical-studies/capita
  16. Pfizer Receives FDA Approval to Extend Use of Prevnar 13® for Prevention of Pneumococcal Pneumonia and Invasive Disease in Adults 50 Years and Older, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_fda_approval_to_extend_use_of_prevnar_13_for_prevention_of_pneumococcal_pneumonia_and_invasive_disease_in_adults_50_years_and_older
  17. Full article: Prevention of adult pneumococcal pneumonia with the 13-valent pneumococcal conjugate vaccine: CAPiTA, the community-acquired pneumonia immunization trial in adults - Taylor & Francis Online, accessed October 1, 2025, https://www.tandfonline.com/doi/full/10.1080/21645515.2015.1043502
  18. About Pneumococcal Vaccines: For Providers - CDC, accessed October 1, 2025, https://www.cdc.gov/vaccines/vpd/pneumo/hcp/about-vaccine.html
  19. Ask The Experts About Vaccines: Pneumococcal | Immunize.org, accessed October 1, 2025, http://www.immunize.org/ask-experts/topic/pneumococcal/
  20. Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults - MDPI, accessed October 1, 2025, https://www.mdpi.com/2076-0817/12/5/732
  21. PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) - MDPI, accessed October 1, 2025, https://www.mdpi.com/2076-2607/10/1/127
  22. A Study Analyzing Observational Data Shows Real-World Effectiveness of Prevnar® 13 in Adults Age 65+ | Pfizer, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/a_study_analyzing_observational_data_shows_real_world_effectiveness_of_prevnar_13_in_adults_age_65-0
  23. Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies | PLOS One, accessed October 1, 2025, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177985
  24. Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023 | MMWR - CDC, accessed October 1, 2025, https://www.cdc.gov/mmwr/volumes/72/rr/rr7203a1.htm
  25. Prevenar 13 | European Medicines Agency (EMA), accessed October 1, 2025, https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-13
  26. Pfizer Receives European Approval To Expand Use Of Prevenar 13* To Adults Aged 18 To 49 Years For The Prevention Of Invasive Pneumococcal Disease | Fierce Pharma, accessed October 1, 2025, https://www.fiercepharma.com/pharma/pfizer-receives-european-approval-to-expand-use-of-prevenar-13-to-adults-aged-18-to-49-years
  27. Pfizer Receives FDA Approval for Prevnar 13® in Adults Age 18 Through 49, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_fda_approval_for_prevnar_13_in_adults_age_18_through_49
  28. Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design - PubMed, accessed October 1, 2025, https://pubmed.ncbi.nlm.nih.gov/29790925/
  29. Clinical Trial Program | PREVNAR 20® (Pneumococcal 20-valent Conjugate Vaccine), accessed October 1, 2025, https://prevnar20adult.pfizerpro.com/clinical-studies
  30. Pneumococcal vaccination effectiveness (PCV13 and PPSV23) in individuals with and without reduced kidney function: a test-negative design study - Oxford Academic, accessed October 1, 2025, https://academic.oup.com/ckj/article/17/6/sfae145/7667367
  31. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study, accessed October 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11288330/
  32. Prevenar 13, INN-Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) - European Medicines Agency, accessed October 1, 2025, https://www.ema.europa.eu/en/documents/product-information/prevenar-13-epar-product-information_en.pdf
  33. Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 | MMWR - CDC, accessed October 1, 2025, https://www.cdc.gov/mmwr/volumes/71/wr/mm7137a3.htm
  34. Package Insert - Prevnar 13 - FDA, accessed October 1, 2025, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert------Prevnar-13.pdf
  35. Pneumococcal Vaccine - StatPearls - NCBI Bookshelf, accessed October 1, 2025, https://www.ncbi.nlm.nih.gov/books/NBK507794/
  36. Who should not get Pneumococcal vaccine?, accessed October 1, 2025, https://www.nvic.org/disease-vaccine/pneumococcal/vaccine-who-should-not-get
  37. Childhood Vaccine Schedule: Immunizations By Age - Cleveland Clinic, accessed October 1, 2025, https://my.clevelandclinic.org/health/articles/11288-childhood-immunization-schedule
  38. Prevnar 13 (pneumococcal vaccine 13-valent) dosing, indications, interactions, adverse effects, and more. - Medscape Reference, accessed October 1, 2025, https://reference.medscape.com/drug/prevnar-13-pneumococcal-vaccine-13-valent-999483
  39. Pneumococcal Vaccine Recommendations | Pneumococcal | CDC, accessed October 1, 2025, https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html
  40. Recommendations for Pneumococcal Vaccines Use in Children and Teens - Immunize.org, accessed October 1, 2025, https://www.immunize.org/wp-content/uploads/catg.d/p2016.pdf
  41. Catch-up Immunization Schedule for Children and Adolescents (Addendum updated August 7, 2025) - CDC, accessed October 1, 2025, https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-catch-up.html
  42. If You're 65 or Older, it's Time to get Your Pneumococcal Shots - New York State Department of Health, accessed October 1, 2025, https://www.health.ny.gov/publications/2406/
  43. Learn More: Pneumococcal Vaccines for Older Adults | HealthInAging.org, accessed October 1, 2025, https://www.healthinaging.org/tools-and-tips/learn-more-pneumococcal-vaccines-older-adults
  44. CDC's Updated Pneumococcal Vaccine Recommendations for Adults - NACCHO, accessed October 1, 2025, https://www.naccho.org/blog/articles/cdcs-updated-pneumococcal-vaccine-recommendations-for-adults
  45. Pneumococcal Vaccine Timing for Adults - CDC, accessed October 1, 2025, https://www.cdc.gov/pneumococcal/downloads/Vaccine-Timing-Adults-JobAid.pdf
  46. Pneumococcal Vaccines: Understanding Centers for Disease Control and Prevention Recommendations - PMC, accessed October 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4213993/
  47. Pneumococcal Vaccine - Infectious Diseases - Merck Manual Professional Edition, accessed October 1, 2025, https://www.merckmanuals.com/professional/infectious-diseases/immunization/pneumococcal-vaccine
  48. Adult Immunization Schedule - AAFP, accessed October 1, 2025, https://www.aafp.org/family-physician/patient-care/prevention-wellness/immunizations-vaccines/immunization-schedules/adult-immunization-schedule.html
  49. Expanded Recommendations for Use of Pneumococcal Conjugate Vaccines Among Adults Aged ≥50 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024 | MMWR - CDC, accessed October 1, 2025, https://www.cdc.gov/mmwr/volumes/74/wr/mm7401a1.htm
  50. PREVNAR 13® (pneumococcal 13-valent conjugate vaccine - diphtheria CRM197 protein) Contraindications | Pfizer Medical - US, accessed October 1, 2025, https://www.pfizermedical.com/prevnar-13/contradictions
  51. Advisory Committee on Immunization Practices Recommends PREVNAR 20® (20-Valent Pneumococcal Conjugate Vaccine) for Adults Aged 50 and Older | Pfizer, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/advisory-committee-immunization-practices-recommends
  52. 8 Prevnar 13 Side Effects and How to Manage Them - GoodRx, accessed October 1, 2025, https://www.goodrx.com/prevnar-13/common-side-effects
  53. Pneumococcal 13-valent vaccine, diphtheria conjugate (intramuscular route) - Side effects & uses - Mayo Clinic, accessed October 1, 2025, https://www.mayoclinic.org/drugs-supplements/pneumococcal-13-valent-vaccine-diphtheria-conjugate-intramuscular-route/description/drg-20074043
  54. Pneumococcal vaccine - NHS, accessed October 1, 2025, https://www.nhs.uk/vaccinations/pneumococcal-vaccine/
  55. Pneumococcal Conjugate Vaccine Safety in Elderly Adults - PMC, accessed October 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6016414/
  56. Prevnar 13 (pneumococcal 13-valent conjugate vaccine) FDA Approval History - Drugs.com, accessed October 1, 2025, https://www.drugs.com/history/prevnar-13.html
  57. Pfizer Receives European Approval For Label Update Regarding The Use Of Prevenar 13 In Certain High-Risk Populations, accessed October 1, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer_receives_european_approval_for_label_update_regarding_the_use_of_prevenar_13_in_certain_high_risk_populations
  58. Australian Public Assessment Report for Pneumococcal Polysaccharide Conjugate Vaccine 13 valent - Therapeutic Goods Administration (TGA), accessed October 1, 2025, https://www.tga.gov.au/sites/default/files/auspar-prevenar-13-111215.pdf
  59. Australian public assessment for Pneumococcal polysaccharide conjugate vaccine, 13-valent adsorbed - Therapeutic Goods Administration (TGA), accessed October 1, 2025, https://www.tga.gov.au/sites/default/files/auspar-pneumococcal-polysaccharide-conjugate-140917_0.pdf

Published at: October 1, 2025

This report is continuously updated as new research emerges.

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