Low Endotoxic and Immunogenic Outer Membrane Vesicle Vaccine Platform Derived from an MsbB-Deficient Salmonella enteritidis Mutant

서지정보

· 발행기관 : 한국실험동물학회
· 수록지 정보 : Laboratory Animal Research / 24권 / 4호 / 649 ~ 657페이지
· 저자명 : 이상래, Kang-Jin Jeong, Sang-Hyun Kim, Keun-Su Kim, Sung-Jin Kim, 김영현, 허재원, Ekyune Kim, Myeong-Su Kim, 서준교, 장규태

초록

A low endotoxic Outer membrane vesicles (OMVs) vaccine platform was established with an msbB genedeleted
(ΔmsbB) Salmonella enteritidis mutant. The Salmonella ΔmsbB mutant displayed lipopolysaccharide
phenotypic changes showing faster migration of the lipid A-core region in an SDS-PAGE analysis and the
increased amount of penta-acyl lipid A due to the MsbB deficiency. In an endotoxicity assay, BALB/c mice
injected intraperitoneally with the Salmonella ΔmsbB mutant survived for 10 days, whereas mice injected
intraperitoneally with the wild type survived for 5 days. Also, all mice inoculated orally with the ΔmsbB
mutant survived for 30 days but 70% of mice inoculated orally with wild type survived. Electron
microscopically, the Salmonella ΔmsbB mutant produced a larger amount of OMVs than the wild type. In
immunogenicity tests, all sera from mice groups immunized with the wild type, ΔmsbB mutant, and their
OMVs, showed significantly higher IgG levels. This result was consistent with higher bactericidal activities
against wild type S. enteritidis, compared to the negative control. However, there were no significant
differences in serum IgG levels and the bactericidal activities of the immune sera between the four mice
groups. The viable counts of S. enteritidis recovered from the spleen and liver of four preimmunized mice
groups after 5 days of the bacterial challenge showed significant reductions of the live bacteria.
Conclusively, the ΔmsbB mutant of S. enteritidis produced relatively low endotoxic OMVs, which was
verified in this study for its potential to be a non-replicating Salmonella vaccine candidate.

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