Bacterial pathogens are the second leading cause of death worldwide. However, the development of bacterial vaccines has been challenged by the presence of multiple serotypes and the lack of cross-protection between serotypes. Therefore, there is an urgent need to identify protective antigens conserved across serotypes in order to develop a broadly protective vaccine. Here, we have developed an unbiased and genome-wide technique, BacScan, which uses bacterial-specific serum to rapidly identify highly conserved immunogenic proteins by combining phage display, immunoprecipitation, and next-generation sequencing. As a proof of concept, we identified 19 highly immunogenic proteins fromStreptococcus suiscore proteins. Immunoreactivity analysis of mouse, pig, and human sera indicated that 2 proteins could be the potential targets for the development of serological diagnostics. Eight proteins provided 20%-100% protection againstS. suischallenge in immunized animals, indicating the potential vaccine targets. BacScan can be applied to any bacterial pathogen and has the potential to accelerate the development of a broadly protective bacterial vaccine.TeaserA novel method to identify the highly conserved immunogenic bacterial proteins as targets for the development a broadly protective bacterial vaccine.
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