BacScan: An Unbiased and Genome-Wide Approach to Identify Bacterial Highly Immunogenic Proteins

Abstract 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 from Streptococcus suis core 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 against S. suis challenge 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. Teaser A novel method to identify the highly conserved immunogenic bacterial proteins as targets for the development a broadly protective bacterial vaccine.