Dual‐Pathogen Defense: Engineering an ExPEC Ghost to Display Protective Epitopes of Streptococcus suis

Streptococcus suis and extraintestinal pathogenic Escherichia coli (ExPEC) cause severe swine infections and major economic losses worldwide. Antimicrobial resistance (AMR) and polymicrobial interactions complicate disease control. Existing vaccine strategies are insufficient to provide broad cross-serotype protection against S. suis strains while simultaneously combating ExPEC infections. We developed a bivalent vaccine platform that integrates bacterial ghost (BG) technology with surface antigen display. By utilizing the porcine ExPEC strain PU-1 as a carrier, which could cause acute sepsis in mouse infection model. Using an Lpp'-OmpA surface display system, we constructed recombinant BGs derived from E. coli that express a multi-epitope antigen against S. suis (MEAS 1), while retaining native E. coli antigenic components as the immunogen against ExPEC. Administration of this vaccine induced robust cellular and humoral immune responses specific to both S. suis and E. coli. The vaccine demonstrated dual protection: 70%-90% survival against S. suis (serotypes 2/9) and 70% against ExPEC challenge in mouse model. Porcine trials demonstrated a significant reduction in bacteremia and provided effective protection against pathogenic challenges. This platform offers a potential solution for preventing infections caused by S. suis and ExPEC.