Identification and evaluation of cross-protection efficiency of the conserved antigens of Salmonella Enteritidis.

Salmonella, a major foodborne zoonotic pathogen, threatens global poultry production and public health. While inactivated vaccines exhibit limited efficacy and live attenuated vaccines raise safety concerns due to risks of virulence reversion, subunit vaccines represent a safer and more targeted alternative. However, existing subunit vaccines against Salmonella provide limited cross-serotype protection. To address this challenge, OmpC, OmpD, OmpF (outer membrane proteins), SseB (a Type III secretory system secretory protein), and FliC (flagellin) were selected as five conserved antigens of Salmonella Enteritidis (S. enteritidis) for evaluation of their immune protective efficacy in this work. Our data showed that all antigens exhibited strong humoral and cell-mediated immune responses specific to each antigen, significantly reducing mortality and bacterial burdens following S. enteritidis challenge compared to infected controls. Notably, the SseB subunit vaccine demonstrated promising but serovar-dependent protection, inducing partial cross-reactive opsonophagocytic antibody (OPA) responses against Salmonella serovars. Protection experiments revealed divergent efficacy: 66.7 % survival against homologous S. enteritidis versus limited 33.3 % survival against heterologous S. typhimurium challenge. Both groups exhibited significantly reduced bacterial colonization and mitigated histopathological damage. These findings position SseB as a key candidate for serovar-specific subunit vaccines, laying the groundwork for multivalent approaches targeting conserved virulence machinery.