The invention relates to immunogenic compositions comprising mutant Streptococcus pneumoniae pneumolysin proteins. The invention further relates to such proteins and nucleic acids encoding these proteins. In particular embodiments, the invention is directed to an isolated mutant pneumolysin (PLY) protein, wherein the mutant PLY protein differs from the wild-type PLY protein of SEQ ID NO:1 presence of a mutation within the region of amino acids 144 to 161 of the wild type such that the toxicity of the mutant is reduced relative to that of the wild-type protein. In particular embodiments, the mutant PLY protein differs from the wild-type protein by the substitution or deletion of amino acids including the deletion of two adjacent amino acids within the region of amino acids 144 to 151 of the wild-type sequence.
