During the last century, several approaches have been used for the development of vaccines, ranging from the immunization with live-attenuated bacteria up to the formulation of the safer sub-unit vaccines. These conventional approaches to vaccine development require cultivation of the pathogen and its dissection using biochemical, immunological and microbiological methods. Although successful in several cases, these methods have failed to provide solutions against many human pathogens. With the impressive progress of bio informatics and high throughput protein expression, three new areas, genomics, transcriptomics, and proteomics, have emerged with the potential to enormously speed up the vaccine discovery process. Each of these approaches leads to the selection of the most relevant proteins for the induction of protective immune responses, e.g. membrane-associated proteins, secreted proteins and virulence factors. Genomic involves the sequencing of a given bacterial genome and the use of various algorithms to predict which genes potentially code for membrane-associated and virulence-associated proteins. Transcriptomics is of particular interest to define virulence factors. It uses DNA micro arrays to measure bacterial gene expression in response to host/pathogen interaction. Proteomics allows the direct identification of potential vaccine candidates through the separation of bacterial membrane-associated proteins (usually by two-dimensional electrophoresis), and the iridentification by mass spectrometry.
Once selected, the potential vaccine candidates are expressed and purified in a high throughput setting and the purified antigens are finally tested in correlate-of-protection assays to select the most promising vaccine candidates. The availability of a large collection of bacterial proteins also allows the identification of most immunogenic antigens using protein microarray technology.
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