Identification of the targets of cross-reactive antibodies induced by Streptococcus pneumoniae colonization

Infect Immun. 2010 May;78(5):2231-9. doi: 10.1128/IAI.01058-09. Epub 2010 Mar 15.

Abstract

Much of the efficacy of current pneumococcal conjugate vaccines lies in their ability to decrease carriage of vaccine serotypes in the population. Novel and more-broadly acting vaccines would also need to target carriage in order to be as effective. We have previously shown that model murine carriage of Streptococcus pneumoniae can elicit antibody-dependent immunity and can protect against a virulent heterologous challenge strain. This study set out to identify S. pneumoniae surface antigens that may elicit cross-reactive antibodies following colonization. Western blot analysis using sera from colonized mice identified the previously characterized immunogens pneumococcal surface protein A (PspA), putative proteinase maturation protein A (PpmA), and pneumococcal surface adhesin A (PsaA) as such antigens. Using flow cytometry, PspA was found to be the major target of surface-bound cross-reactive IgG in sera from TIGR4 Delta cps-colonized mice, with a modest contribution from PpmA and none from PsaA. In human sera, however, only mutants lacking PpmA were shown to have reduced binding of surface IgG compared to wild-type strains, suggesting that prior exposure to S. pneumoniae in humans may induce PpmA antibodies. We also investigated if cross-reactive antibodies induced by these antigens may be cross-protective against carriage. Despite the immunogenicity of PspA, PpmA, and PsaA, mice were still protected following colonization with mutants lacking these antigens, suggesting they are not necessary for cross-protection induced by carriage. Our findings suggest that a whole-organism approach may be needed to broadly diminish carriage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / immunology
  • Animals
  • Antibodies, Bacterial / immunology*
  • Antibodies, Bacterial / metabolism
  • Bacterial Proteins / immunology
  • Blotting, Western
  • Carrier State / immunology
  • Carrier State / prevention & control*
  • Colony Count, Microbial
  • Cross Reactions*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Lipoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / prevention & control*
  • Protein Binding
  • Streptococcus pneumoniae / immunology*
  • Survival Analysis

Substances

  • Adhesins, Bacterial
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Immunoglobulin G
  • Lipoproteins
  • PpmA protein, Streptococcus pneumoniae
  • PsaA protein, Streptococcus
  • pneumococcal surface protein A