Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines

Scand J Immunol. 2005 Apr;61(4):322-8. doi: 10.1111/j.1365-3083.2005.01584.x.

Abstract

The immune response to polysaccharides is initiated when polysaccharides bind complement factor C3d, and these polysaccharide-C3d complexes subsequently localize on splenic marginal zone B cells strongly expressing CD21 (complement receptor 2). Infants and children under the age of 2 years have low or absent expression of CD21 on their marginal zone B cells, and consequently do not adequately respond to polysaccharides. In contrast, polysaccharide-protein conjugate vaccines are able to induce antibodies at this young age. Conjugate vaccines apparently overcome the necessity for CD21-C3d interaction for an antipolysaccharide immune response. We demonstrate in a rat model that localization of pneumococcal polysaccharides on splenic marginal zone B cells indeed is complement dependent. We also show that pneumococcal conjugates do not specifically localize on splenic marginal zone B cells and that splenic localization of polysaccharide conjugates is independent of the presence of complement. Thus, the induction of antipolysaccharide antibodies by conjugate vaccines apparently can occur independently of CD21-C3d interaction. These basic findings may explain the effectiveness of conjugated vaccines in young children and may open the way for their application in other patient groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Complement C3d / immunology*
  • Complement C3d / metabolism
  • Complement Pathway, Classical / immunology
  • Elapid Venoms / immunology
  • Immunohistochemistry
  • Liver / immunology
  • Male
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / immunology*
  • Pneumococcal Vaccines / pharmacokinetics
  • Polysaccharides, Bacterial / blood
  • Polysaccharides, Bacterial / immunology*
  • Polysaccharides, Bacterial / metabolism
  • Rats
  • Rats, Wistar
  • Spleen / immunology*
  • Spleen / metabolism
  • Streptococcus pneumoniae / immunology*
  • Vaccination / methods*
  • Vaccines, Conjugate / immunology
  • Vaccines, Conjugate / metabolism

Substances

  • Elapid Venoms
  • Pneumococcal Vaccines
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • Complement C3d