The potential devastation resulting from an intentional outbreak caused by biological warfare agents such as Brucella abortus and Bacillus anthracis underscores the need for next generation vaccines. Proteomics, genomics, and systems biology approaches coupled with the bacterial ghost (BG) vaccine delivery strategy offer an ideal approach for developing safer, cost-effective, and efficacious vaccines for human use in a relatively rapid time frame. Critical to any subunit vaccine development strategy is the identification of a pathogen's proteins with the greatest potential of eliciting a protective immune response. These proteins are collectively referred to as the pathogen's immunome. Proteomics provides high-resolution identification of these immunogenic proteins using standard proteomic technologies, Western blots probed with antisera from infected patients, and the pathogen's sequenced and annotated genome. Selected immunoreactive proteins can be then cloned and expressed in nonpathogenic Gram-negative bacteria. Subsequently, a temperature shift or chemical induction process is initiated to induce expression of the PhiX174 E-lysis gene, whose protein product forms an E tunnel between the inner and outer membrane of the bacteria, expelling all intracellular contents. The BG vaccine system is a proven strategy developed for many different pathogens and tested in a complete array of animal models. The BG vaccine system also has great potential for producing multiagent vaccines for protection to multiple species in a single formulation.