Abstract
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 ΔompA, ΔompC, and ΔompD, and determined the protection effectiveness of these candidate vaccines in murine and chicken infection models. The results showed that ΔompA led to an increase in the production of OMVs. Notably, ΔompAΔompCΔompD 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 ΔompA OMVs. Subsequently, we verified the results in the chicken model, in which ΔompAΔompCΔompD 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.
Highlights
Salmonella and avian pathogenic Escherichia coli (APEC) are both important pathogens that can cause extended and acute bacterial disease, such as avian colibacillosis and fowl typhoid, and even death in poultry, especially in chickens, worldwide (Barrow, 2007; Whiley and Ross, 2015)
Cryo-EM data showed that Outer membrane vesicle (OMV) purified from the ΔompAΔompCΔompD mutant strains were spherical, and no other contaminant was visible, which indicated that deletion of major outer membrane protein (OMP) did not affect the structure of OMV particles (Supplementary Figure 2)
The results showed that the majority of the produced OMVs derived from omp mutant strains and parental strain had a diameter of 70–90 nm, and the highest concentration of particles was in consecutive fractions 25 and 30% OptiPrep (Supplementary Figures 3, 4), which indicated that the omp knockout mutants did not affect the particle size of OMVs secreted by the bacteria
Summary
Salmonella and avian pathogenic Escherichia coli (APEC) are both important pathogens that can cause extended and acute bacterial disease, such as avian colibacillosis and fowl typhoid, and even death in poultry, especially in chickens, worldwide (Barrow, 2007; Whiley and Ross, 2015). Salmonella infections are a concern for the global poultry industry and a threat to the health and safety of human populations worldwide. The diseases induced by Salmonella and APEC are difficult to control because of numerous serotypes of the pathogens (Gast, 2007; Ebrahimi-Nik et al, 2018). Immunization with multiple or multivalent vaccines is often necessary to obtain a protective effect against these bacteria. Continuous screening for effective vaccine candidates should be performed as a safer and more effective way to improve the effectiveness of cross-protective immunity
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