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Lipopolysaccharide (LPS) is a major virulence factor present in the outer membrane of  Salmonella enterica  serovar Typhimurium ( S.  Typhimurium). Outer membrane proteins (OMPs) from  Salmonella  show high immunogenicity and provide protection against  Salmonella  infection, and truncated LPS alters the outer membrane composition of the cell wall. In our previous study, we demonstrated that  Salmonella  mutants carrying truncated LPS failed to induce strong immune responses and cross-reaction to other enteric bacteria, due to their high attenuation and low colonization in the host. Therefore, we plan to investigate whether outer membrane proteins from  Salmonella  mutants with truncated LPS resulting from a series of nonpolar mutations, including ∆ waaC12 , ∆ waaF15 , ∆ waaG42 , ∆ rfaH49 , ∆ waaI43 , ∆ waaJ44 , ∆ waaL46 , ∆ wbaP45  and ∆ wzy-48 , affect immunogenicity and provide protection against diverse  Salmonella  challenge. In this study, the immunogenicity and cross-protection efficiency of purified OMPs from all mutants were investigated to explore a potential OMP vaccine to protect against homologous or heterologous serotype  Salmonella  challenge. The results demonstrated that OMPs from three  Salmonella  mutants (∆ waaC12 , ∆ waaJ44  and ∆ waaL46 ) induced higher immune responses and provided good protection against homologous  S.  Typhimurium. The OMPs from these three mutants were also selected to determine the cross-protective efficacy against homologous and heterologous serotype  Salmonella . Our results indicated that the mutant ∆ waaC12  can elicit higher cross-reactivity and can provide good protection against  S.  Choleraesuis and  S.  Enteritidis infection and that the cross-reactivity may be ascribed to an antigen of approximately 18.4–30 kDa.

Immunogenicity and Cross-Protective Efficacy Induced by Outer Membrane Proteins from Salmonella Typhimurium Mutants with Truncated LPS in Mice