AUTHOR=Chen Yuxuan , Jie Kaiwen , Li Biaoxian , Yu Haiyan , Ruan Huan , Wu Jing , Huang Xiaotian , Liu Qiong 

TITLE=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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.588952

DOI=10.3389/fmicb.2020.588952

ISSN=1664-302X

ABSTRACT=<p>Colibacillosis is an economically important infectious disease in poultry, caused by avian pathogenic <italic>Escherichia coli</italic> (APEC). <italic>Salmonella enterica</italic> serovar Enteritidis (<italic>S.</italic> 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 <italic>S. enterica</italic> serovar Typhimurium mutants with a remodeled outer membrane could induce cross-protection against heteroserotypic <italic>Salmonella</italic> 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<italic>ompA</italic>, Δ<italic>ompC</italic>, and Δ<italic>ompD</italic>, and determined the protection effectiveness of these candidate vaccines in murine and chicken infection models. The results showed that Δ<italic>ompA</italic> led to an increase in the production of OMVs. Notably, Δ<italic>ompA</italic>Δ<italic>ompC</italic>Δ<italic>ompD</italic> OMVs showed significantly better cross-protection against <italic>S. enterica</italic> serovar Choleraesuis, <italic>S.</italic> Enteritidis, APEC O78, and <italic>Shigella flexneri</italic> 2a than did other <italic>omp</italic>-deficient OMVs, with the exception of Δ<italic>ompA</italic> OMVs. Subsequently, we verified the results in the chicken model, in which Δ<italic>ompA</italic>Δ<italic>ompC</italic>Δ<italic>ompD</italic> OMVs elicited significant cross-protection against <italic>S.</italic> 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.</p>