IMMUNIZATION OF MICE WITH PNEUMOLYSIN TOROID CONFERS A SIGNIFICANT DEGREE OF PROTECTION AGAINST AT LEAST 9 SEROTYPES OF STREPTOCOCCUS-PNEUMONIAE

Pneumolysin is the thiol-activated cytolysin produced by Streptococcus pneumoniae. Mice were immunized with a genetically engineered toroid version of pneumolysin, which was derived from a serotype 2 pneumococc us. The toroid carried the mutation Trp-433-->Phe. Alum was used as th e adjuvant. Immunized mice had significantly increased levels of anti- pneumolysin antibodies, principally immunoglobulin GI. Mice were chall enged intraperitoneally or intranasally with 12 strains covering capsu lar serotypes 1 to 6, 7F, 8, and 18C. Following challenge, the surviva l rate and/or the time of death of nonsurvivors (survival time) was si gnificantly greater than that of sham-immunized mice for all nine sero types. However, differences in the degree of protection were noted bet ween different strains. The route of challenge also appeared to influe nce 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 co nsideration for inclusion in a human vaccine.