Protection against pneumococcal pneumonia in mice by monoclonal antibodies to pneumolysin

Infect Immun. 2004 Aug;72(8):4534-40. doi: 10.1128/IAI.72.8.4534-4540.2004.

Abstract

Pneumolysin (PLY) is an important virulence factor of Streptococcus pneumoniae. We examined the ability of three murine monoclonal antibodies (MAbs) to PLY (PLY-4, PLY-5, and PLY-7) to affect the course of pneumococcal pneumonia in mice. The intravenous administration of antibodies PLY-4 and PLY-7 protected the mice from the lethal effect of the purified toxin. Mice treated with PLY-4 before intranasal inoculation of S. pneumoniae type 2 survived longer (median survival time, 100 h) than did untreated animals (median survival time, 60 h) (P < 0.0001). The median survival time for mice treated with a combination of PLY-4 and PLY-7 was 130 h, significantly longer than that for mice given isotype-matched indifferent MAbs (P = 0.0288) or nontreated mice (P = 0.0002). The median survival time for mice treated with a combination of three MAbs was significantly longer (>480 h) than that for mice treated with PLY-5 (48 h; P < 0.0001), PLY-7 (78 h; P = 0.0007), or PLY-4 (100 h; P = 0.0443) alone. Similarly, the survival rate for mice treated with three MAbs (10 of 20 mice) was significantly higher than the survival rate obtained with PLY-5 (1 of 20; P = 0.0033), PLY-4 (2 of 20; P = 0.0138), or PLY-7 (3 of 20; P = 0.0407) alone. These results suggest that anti-PLY MAbs act with a synergistic effect. Furthermore, MAb administration was associated with a significant decrease in bacterial lung colonization and lower frequencies of bacteremia and tissue injury with respect to the results for the control groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / administration & dosage*
  • Antibodies, Bacterial / immunology
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Bacteremia / mortality
  • Bacteremia / prevention & control
  • Bacterial Proteins
  • Blood / microbiology
  • Drug Synergism
  • Humans
  • Immunization, Passive
  • Injections, Intravenous
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Neutralization Tests
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology
  • Pneumonia, Pneumococcal / mortality
  • Pneumonia, Pneumococcal / pathology
  • Pneumonia, Pneumococcal / prevention & control*
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / pathogenicity
  • Streptolysins / administration & dosage
  • Streptolysins / immunology*
  • Streptolysins / toxicity

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Bacterial Proteins
  • Pneumococcal Vaccines
  • Streptolysins
  • plY protein, Streptococcus pneumoniae