Cargando…

Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles

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 tox...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, Kyoung Sub, Kim, Sang-Hyun, Kim, Eun-Do, Lee, Sang-Ho, Han, Soo Jung, Yoon, Sangchul, Chang, Kyu-Tae, Seo, Kyoung Yul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102476/
https://www.ncbi.nlm.nih.gov/pubmed/25032703
http://dx.doi.org/10.1371/journal.pone.0100229
_version_ 1782481045009989632
author Choi, Kyoung Sub
Kim, Sang-Hyun
Kim, Eun-Do
Lee, Sang-Ho
Han, Soo Jung
Yoon, Sangchul
Chang, Kyu-Tae
Seo, Kyoung Yul
author_facet Choi, Kyoung Sub
Kim, Sang-Hyun
Kim, Eun-Do
Lee, Sang-Ho
Han, Soo Jung
Yoon, Sangchul
Chang, Kyu-Tae
Seo, Kyoung Yul
author_sort Choi, Kyoung Sub
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4102476
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41024762014-07-21 Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles Choi, Kyoung Sub Kim, Sang-Hyun Kim, Eun-Do Lee, Sang-Ho Han, Soo Jung Yoon, Sangchul Chang, Kyu-Tae Seo, Kyoung Yul PLoS One Research Article 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. Public Library of Science 2014-07-17 /pmc/articles/PMC4102476/ /pubmed/25032703 http://dx.doi.org/10.1371/journal.pone.0100229 Text en © 2014 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Choi, Kyoung Sub
Kim, Sang-Hyun
Kim, Eun-Do
Lee, Sang-Ho
Han, Soo Jung
Yoon, Sangchul
Chang, Kyu-Tae
Seo, Kyoung Yul
Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title_full Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title_fullStr Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title_full_unstemmed Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title_short Protection from Hemolytic Uremic Syndrome by Eyedrop Vaccination with Modified Enterohemorrhagic E. coli Outer Membrane Vesicles
title_sort protection from hemolytic uremic syndrome by eyedrop vaccination with modified enterohemorrhagic e. coli outer membrane vesicles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102476/
https://www.ncbi.nlm.nih.gov/pubmed/25032703
http://dx.doi.org/10.1371/journal.pone.0100229
work_keys_str_mv AT choikyoungsub protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT kimsanghyun protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT kimeundo protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT leesangho protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT hansoojung protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT yoonsangchul protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT changkyutae protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles
AT seokyoungyul protectionfromhemolyticuremicsyndromebyeyedropvaccinationwithmodifiedenterohemorrhagicecolioutermembranevesicles