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Colibacillosis is an economically important infectious disease in poultry, caused by avian pathogenic  Escherichia coli  (APEC).  Salmonella enterica  serovar Enteritidis ( S.  Enteritidis) is a major cause of food-borne diseases in human circulated through poultry-derived products, including meat and chicken eggs. Vaccine control is the mainstream approach for combating these infections, but it is difficult to create a vaccine for the broad-spectrum protection of poultry due to multiple serotypes of these pathogens. Our previous studies have shown that outer membrane vesicles (OMVs) derived from  S. enterica  serovar Typhimurium mutants with a remodeled outer membrane could induce cross-protection against heteroserotypic  Salmonella  infection. Therefore, in this study, we further evaluated the potential of broad-spectrum vaccines based on major outer membrane protein (OMP)-deficient OMVs, including Δ ompA , Δ ompC , and Δ ompD , and determined the protection effectiveness of these candidate vaccines in murine and chicken infection models. The results showed that Δ ompA  led to an increase in the production of OMVs. Notably, Δ ompA Δ ompC Δ ompD  OMVs showed significantly better cross-protection against  S. enterica  serovar Choleraesuis,  S.  Enteritidis, APEC O78, and  Shigella flexneri  2a than did other  omp -deficient OMVs, with the exception of Δ ompA  OMVs. Subsequently, we verified the results in the chicken model, in which Δ ompA Δ ompC Δ ompD  OMVs elicited significant cross-protection against  S.  Enteritidis and APEC O78 infections. These findings further confirmed the feasibility of improving the immunogenicity of OMVs by remodeling the outer membrane and provide a new perspective for the development of broad-spectrum vaccines based on OMVs.

frontiers in microbiology

Immunization With Outer Membrane Vesicles Derived From Major Outer Membrane Protein-Deficient Salmonella Typhimurium Mutants for Cross Protection Against Salmonella Enteritidis and Avian Pathogenic Escherichia coli O78 Infection in Chickens