Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children

Vaccine. 2014 Jan 9;32(3):417-24. doi: 10.1016/j.vaccine.2013.11.029. Epub 2013 Dec 2.


Background: Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

Objective: To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

Methods: Children (n=89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13 (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

Results: One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

Conclusions: PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.

Trial registration: NCT00853749.

Keywords: Antibody persistence; Conjugate vaccine; Hyporesponsiveness; Memory; Pneumococcus; Polysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibody Affinity
  • Child
  • Drug Interactions*
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Opsonin Proteins / blood
  • Phagocytosis
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / immunology*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology


  • Antibodies, Bacterial
  • Immunoglobulin G
  • Opsonin Proteins
  • Pneumococcal Vaccines
  • Vaccines, Conjugate

Associated data

  • EudraCT/2008-006194-33