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Protection from hemolytic uremic syndrome by eyedrop vaccination with modified enterohemorrhagic E. coli outer membrane vesicles

 Kyoung Sub Choi  ;  Sang-Hyun Kim  ;  Eun-Do Kim  ;  Sang-Ho Lee  ;  Soo Jung Han  ;  Sangchul Yoon  ;  Kyu-Tae Chang  ;  Kyoung Yul Seo 
 PLOS ONE, Vol.9(7) : e100229, 2014 
Journal Title
Issue Date
Animals ; Antibodies, Bacterial/immunology ; Antibody Formation/immunology ; Bacterial Outer Membrane Proteins/administration & dosage ; Bacterial Outer Membrane Proteins/immunology ; Bacterial Outer Membrane Proteins/therapeutic use* ; Blood Urea Nitrogen ; Creatinine/blood ; Escherichia coli Infections/immunology ; Escherichia coli O157/immunology ; Escherichia coli O157/metabolism ; Escherichia coli Proteins/immunology ; Escherichia coli Proteins/therapeutic use* ; Escherichia coli Vaccines/immunology ; Hemolytic-Uremic Syndrome/drug therapy ; Hemolytic-Uremic Syndrome/immunology ; Hemolytic-Uremic Syndrome/prevention & control* ; Immunity, Mucosal/immunology ; Mice ; Mice, Inbred BALB C ; O Antigens/immunology ; Ophthalmic Solutions/administration & dosage ; Ophthalmic Solutions/therapeutic use* ; Vaccination/methods*
We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs) is effective for protecting against hemolytic uremic syndrome (HUS) caused by enterohemorrhagic E. coli (EHEC) O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA)-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB). Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs) at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN)/Creatinin (Cr) were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB) subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.
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1. College of Medicine (의과대학) > Dept. of Medical Humanities and Social Sciences (인문사회의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Do(김은도)
Seo, Kyoung Yul(서경률) ORCID logo https://orcid.org/0000-0002-9855-1980
Yoon, Sang Chul(윤상철) ORCID logo https://orcid.org/0000-0003-0454-9597
Han, Soo Jung(한수정)
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