Enterohemorrhagic Escherichia coli trivalent recombinant vaccine containing EspA, intimin and Stx2 induces strong humoral immune response and confers protection in mice

Enterohemorrhagic Escherichia coli (EHEC) is an important food-borne pathogen, which causes a wide spectrum of diseases ranging from hemorrhagic colitis to life-threatening hemolytic uremic syndrome (HUS). Currently, insufficient measures to prevent and treat EHEC infection make a vaccine against EHEC in great demand. EspA (E. coli secreted protein A), intimin, and Stx2 (Shiga toxin 2) are three predominant virulence factors of EHEC, and each of them has proved to be capable of inducing partial protective immunity. In this study, we constructed a trivalent recombinant protein designated EIS that is composed of EspA (E), C-terminal 300 amino acids of intimin (I) and B subunit of Stx2 (S), and tested it as vaccine using a mouse model. Our results showed that immunization of EIS induced strong humoral response to EspA, intimin and Stx2 and protected mice against the challenges with live EHEC or EHEC sonicated lysate. Moreover, it enhanced clearance of intestinally colonized bacteria. This work suggests that for EHEC vaccines using a combination of EspA, intimin and Stx2 antigens appears to be more effective than using any of these immunogens alone.