The invention relates to immunogenic compositions comprising mutantStreptococcus pneumoniae pneumolysin proteins. The invention further relatesto such proteins and nucleic acids encoding these proteins. In particularembodiments, the invention is directed to an isolated mutant pneumolysin (PLY)protein, wherein the mutant PLY protein differs from the wild type PLY proteinby the presence of a mutation within the region of amino acids 144 to 161 ofthe wild type sequence, such that the toxicity of the mutant is reducedrelative to that of the wild-type protein. In particular embodiments, themutant PLY protein differs from the wild type protein by the substitution ordeletion of amino acids within this region, including the deletion of twoadjacent amino acids within the region of amino acids 144 to 151 of the wildtype sequence.
