Adjuvant activity of outer membrane vesicles from Salmonella minnesota Re595 with lipopolysaccharides modified for attenuating toxicity

Abstract:

[Objective] Outer membrane vesicles (OMVs) are spherical bilayer membrane structures secreted by Gram-negative and some Gram-positive bacteria. OMVs contain abundant surface antigens and are of great research significance in vaccine development. However, the presence of lipopolysaccharides (LPS), which is the primary component of OMVs, arouses safety concern. Therefore, genetically modifying bacterial LPS to produce safe and efficient OMVs is a viable approach to enhance the production and application of OMVs. [Methods] We modified Salmonella minnesota Re595 with O antigen and most core antigen deletions by deleting the acyl chain coding gene msbB and inserting the phosphatase coding gene lpxE from Francisella novicida to reduce acyl chains and phosphate groups on lipid A, thus obtaining less toxic LPS. LPS and OMVs were extracted from the starting strain and modified strain, and their pro-inflammatory activities were compared between the two strains. In addition, inactivated foot-and-mouth disease virus vaccines were prepared with OMVs to assess the immune adjuvant activity of OMVs. [Results] The modification of LPS reduced the endotoxin activity and pro-inflammatory responses while significantly increasing the immune adjuvant activity of OMVs. [Conclusion] This study demonstrates that the modification of LPS can attenuate the toxicity and enhance the immune adjuvant activity of bacterial OMVs. These findings provide a theoretical foundation for utilizing OMVs as immune adjuvants in the future.