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Effective vaccines could provide long-term solutions to many important infectious diseases, however, vaccine development has been hampered by the slow identification of protective antigens. Proteomics provides global information about relevant antigen properties and thus might be ideally suited for identifying promising vaccine antigen subsets. Helicobacter pylori proteomics data are stored in a proteomics database (http://www.mpiib-berlin.mpg.de/2D-PAGE/). In this review, we describe how a combined Helicobacter subproteome analysis resulted in the rapid identification of novel, highly protective antigens. This illustrates the great potential of pathogen proteomics for vaccine development.