Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection

Microbial targets for protective humoral immunity are typically surface-loc alized proteins and contain common sequence motifs related to their secreti on or surface binding. Exploiting the whole genome sequence of the human ba cterial pathogen Streptococcus pneumoniae, we identified 130 open reading f rames encoding proteins with secretion motifs or similarity to predicted vi rulence factors. Mice were immunized with 108 of these proteins, and 6 conf erred protection against disseminated S. pneumoniae infection. Flow cytomet ry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogeni city during human infection. Our results validate the use of a genomic appr oach for the identification of novel microbial targets that elicit a protec tive immune response. These new antigens may play a role in the development of improved vaccines against S. pneumoniae.