What is the difference between Pneumococcal Conjugate Vaccine (PCV) and Pneumococcal Polysaccharide Vaccine (PPSV)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 26, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Key Differences Between PCV and PPSV Vaccines

The fundamental difference is that pneumococcal conjugate vaccines (PCV) induce T-cell dependent immune responses with memory B-cell formation, providing stronger and longer-lasting protection, while pneumococcal polysaccharide vaccines (PPSV) induce T-cell independent responses without immunologic memory, resulting in shorter duration of protection. 1

Immunologic Mechanism

PCV (Conjugate Vaccines)

  • Polysaccharides are chemically conjugated to a carrier protein (CRM197), which activates T-helper cells and creates memory B-cells 1
  • This T-cell dependent response generates both stronger primary responses and robust booster responses upon re-vaccination 2, 3
  • PCV induces significantly higher functional antibody activity (measured by opsonophagocytic killing) compared to PPSV23 for the majority of shared serotypes 3, 4

PPSV23 (Polysaccharide Vaccine)

  • Contains free polysaccharide antigens without protein conjugation 5
  • Induces T-cell independent immune responses that do not create memory B-cells, leading to potentially shorter protection duration 1
  • Re-vaccination with PPSV23 after initial PPSV23 results in lower antibody responses (hyporesponsiveness) for most serotypes compared to the initial dose 2

Clinical Effectiveness Differences

Carriage Reduction

  • PCVs reduce nasopharyngeal carriage of pneumococci, creating herd immunity effects beyond direct protection 1
  • PPSV23 does not reduce bacterial carriage 1

Age-Specific Efficacy

  • PPSV23 is completely ineffective in children under 2 years because they cannot mount adequate immune responses to T-independent polysaccharide antigens 5, 1
  • PCVs are effective even in infants due to their T-cell dependent mechanism 1

Functional Antibody Response

  • PCV13 demonstrated statistically significantly higher opsonophagocytic activity (OPA) titers than PPSV23 for 8 of 12 shared serotypes in vaccine-naive adults aged 60-64 years 3
  • In patients with COPD, PCV7 produced superior functional antibody activity compared to PPSV23 for 6 of 7 serotypes 4

Serotype Coverage

Current Formulations

  • PPSV23 covers 23 serotypes (1,2,3,4,5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F) 5
  • PCV13 covers 13 serotypes 5
  • PCV15 covers 15 serotypes (PCV13 serotypes plus 22F and 33F) 6, 7
  • PCV20 covers 20 serotypes 5, 6

Coverage vs. Quality Trade-off

  • While PPSV23 covers more serotypes numerically, conjugate vaccines provide superior quality protection for the serotypes they do cover 1

Sequential Vaccination Effects

PCV First, Then PPSV23

  • Initial vaccination with PCV establishes immune memory that results in robust recall responses when PPSV23 is subsequently administered 2
  • Adults initially given PCV13 who later received PPSV23 had significantly higher OPA titers for 10 of 13 serotypes compared to those who received PPSV23 as their first vaccine 2

PPSV23 First, Then PCV

  • When PPSV23 is given first, subsequent PPSV23 revaccination yields significantly lower responses for 9 of 13 serotypes compared to initial responses 2
  • Current ACIP guidance recommends PCV15 or PCV20 can be given ≥1 year after PPSV23 for adults who previously received only PPSV23 5, 6

Current Recommendations (2023 ACIP)

For Adults ≥65 Years

  • Either PCV20 alone OR PCV15 followed by PPSV23 (≥1 year later for most adults, minimum 8 weeks for immunocompromised) 5, 6

For High-Risk Adults 19-64 Years

  • Same approach as adults ≥65 years 5

For Children 2-5 Years with Risk Factors

  • PCV13 (or PCV15) followed by PPSV23 at least 2 months later 1

Critical Pitfalls to Avoid

  • Never use PPSV23 alone in children under 2 years—it provides no protection in this age group 5, 1
  • Always administer PCV before PPSV23 when both are indicated to optimize immune response 1, 8
  • Do not assume PPSV23's broader serotype coverage makes it superior—the conjugate vaccines' immunologic advantages outweigh the numerical serotype difference 1
  • Recognize that prior PPSV23 vaccination and older age reduce responsiveness to subsequent pneumococcal vaccination 2, 4

Related Questions

What vaccine is most appropriate to administer to a 64-year-old male with Chronic Obstructive Pulmonary Disease (COPD) who received the 20-valent pneumococcal conjugate vaccine (PCV20) 2 months ago?
What is the most appropriate pneumococcal vaccination regimen for a 42-year-old patient with Chronic Obstructive Pulmonary Disease (COPD), Gold stage 1, and up-to-date vaccinations?
Is a booster dose of Pneumovax23 (Pneumococcal Polysaccharide Vaccine) recommended for a 71-year-old female who received Prevnar13 (Pneumococcal Conjugate Vaccine) 6 years ago and Pneumovax23 13 years ago?
Should a 64-year-old female with allergies and low pneumococcal titers receive the Pneumovax (pneumococcal conjugate vaccine) shot?
What pneumococcal vaccines (Streptococcus pneumoniae vaccines) are available at USA outpatient clinics?
What is an antigen?
What is the best course of action for an adult patient with a history of cardiovascular disease, presenting with constant pitting lower leg edema that persists even after laying flat all night?
What are the treatment options for candidiasis (fungal infection) of the skin in patients with or without underlying medical conditions or compromised immune systems?
What is the ICD-10 (International Classification of Diseases, 10th Revision) code for a mole on the nose that requires a referral to dermatology?
What is the recommended treatment for a pediatric patient with Henoch-Schönlein Purpura (HSP)?
What is the best approach for a patient with a positive Fecal Occult Blood Test (FOBT) result, suspected hemorrhoidal bleeding, and a history of non-compliance with Gastrointestinal (GI) workup due to refusal of bowel prep, for outpatient follow-up with a GI specialist?

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.