Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae

J E Alexander, R A Lock, C C Peeters, J T Poolman, P W Andrew, T J Mitchell, D Hansman, J C Paton

Research output: Contribution to journalArticlepeer-review

182 Citations (Scopus)

Abstract

Pneumolysin is the thiol-activated cytolysin produced by Streptococcus pneumoniae. Mice were immunized with a genetically engineered toxoid version of pneumolysin, which was derived from a serotype 2 pneumococcus. The toxoid carried the mutation Trp-433-->Phe. Alum was used as the adjuvant. Immunized mice had significantly increased levels of anti-pneumolysin antibodies, principally immunoglobulin G1. Mice were challenged intraperitoneally or intranasally with 12 strains covering capsular serotypes 1 to 6, 7F, 8, and 18C. Following challenge, the survival rate and/or the time of death of nonsurvivors (survival time) was significantly greater than that of sham-immunized mice for all nine serotypes. However, differences in the degree of protection were noted between different strains. The route of challenge also appeared to influence the degree of protection. Nevertheless, the significant, albeit in some cases partial, protection provided against all nine pneumococcal serotypes supports the conclusion that pneumolysin toxoids warrant consideration for inclusion in a human vaccine.

Original languageEnglish
Pages (from-to)5683-8
Number of pages6
JournalInfection and Immunity
Volume62
Issue number12
Publication statusPublished - Dec 1994

Keywords

  • Adjuvants, Immunologic
  • Alum Compounds
  • Animals
  • Antibodies, Bacterial
  • Bacterial Capsules
  • Bacterial Proteins
  • Bacterial Vaccines
  • Female
  • Hemolysis
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Pneumococcal Infections
  • Serotyping
  • Species Specificity
  • Streptococcus pneumoniae
  • Streptolysins
  • Toxoids
  • Vaccination
  • Vaccines, Synthetic

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