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In this study, a dual antigen expression cassette consisting of SS2-SaoA and SS9-Eno was delivered by a recombinant <jats:italic>Salmonella<\/jats:italic> Choleraesuis vector to form the vaccine candidate rSC0016(pS-SE). SaoA and Eno were simultaneously synthesized in rSC0016(pS-SE) without affecting the colonization of the recombinant vector in the lymphatic system. In addition, the antiserum of mice immunized with rSC0016(pS-SE) produced a broader and potent opsonophagocytic response against multiple serotypes of <jats:italic>S. suis<\/jats:italic>. Finally, rSC0016(pS-SE) provided mice with a 100% protection against a lethal dose of parent <jats:italic>S. suis<\/jats:italic> serotype 2 and serotype 9, and provided 90% and 80% protection against heterologous <jats:italic>S. suis<\/jats:italic> serotype 7 or 1\/2. These values were significantly higher than those obtained with rSC0016(pS-SaoA) or rSC0016(pS-Eno). 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