Subcutaneous and intranasal immunization with Stx2B–Tir–Stx1B–Zot reduces colonization and shedding of Escherichia coli O157:H7 in mice

Zhang, Xuehan; He, Kongwang; Zhang, Shuxia; Lu, Wei-cai; Zhao, Pandeng; Luan, Xiaoting; Ye, Qing; Li, Wen; Li, Bin; Guo, Ruiyun; Wang, Xiaomin; Lv, Lei; Zhou, Junming; Yu, Zhengyu; Mao, Aihua

doi:10.1016/j.vaccine.2011.02.007

Cited by 32 publications

(29 citation statements)

References 29 publications

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“…Many studies have focused on protein fusions of different virulence factors. Some recent examples include fusions of Stx1B and an inactivated Stx2A (SAmB), Stx2B-Tir-Stx1B-zot (zot; mucosal delivery protein), Stx2B-Stx1B-initimin (SSI), and EspAinitimin-Stx2 (EIS), all of which have shown either reduced STEC shedding or protected against STEC or Stx1/Stx2 challenge in mice (399)(400)(401)(402). Different delivery mechanisms for potential vaccines have also been explored, such as the EspA-intimin-Tir fusion that is expressed in tobacco leaves and canola seeds, Salmonella expressing intimin or EIS, and Stx2B expressed in the Mycobacterium bovis BCG vaccine strain (401,(403)(404)(405).…”

Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli .

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Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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“…Fusion proteins comprising of Stx-derived peptides and T3SS-related proteins are promising vaccine candidates. St2B-Tir-Stx1B-Zot, Stx2B-Stx1B-Int281, EspAStx2A1, EspA-IntiminC300-Stx2B, and Stx2B-BLS fusions have been demonstrated to reduce EHEC colonization in animal models, such as mice and goats (20)(21)(22)(23)(24)(25)(26)(27). Overall, cumulative information indicates that mucosal delivery routes seem to be an effective way to induce immune responses to block the adhesion of EHEC in the intestine, mainly through expression of secretory immunoglobulin A (sIgA) (4).…”

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confidence: 97%

Comparative Genomics and Immunoinformatics Approach for the Identification of Vaccine Candidates for Enterohemorrhagic Escherichia coli O157:H7

García-Angulo

Kalita

et al. 2014

Infect Immun

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c Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains are major human food-borne pathogens, responsible for bloody diarrhea and hemolytic-uremic syndrome worldwide. Thus far, there is no vaccine for humans against EHEC infections. In this study, a comparative genomics analysis was performed to identify EHEC-specific antigens useful as potential vaccines. The genes present in both EHEC EDL933 and Sakai strains but absent in nonpathogenic E. coli K-12 and HS strains were subjected to an in silico analysis to identify secreted or surface-expressed proteins. We obtained a total of 65 gene-encoding protein candidates, which were subjected to immunoinformatics analysis. Our criteria of selection aided in categorizing the candidates as high, medium, and low priority. Three members of each group were randomly selected and cloned into pVAX-1. Candidates were pooled accordingly to their priority group and tested for immunogenicity against EHEC O157:H7 using a murine model of gastrointestinal infection. The high-priority (HP) pool, containing genes encoding a Lom-like protein (pVAX-31), a putative pilin subunit (pVAX-12), and a fragment of the type III secretion structural protein EscC (pVAX-56.2), was able to induce the production of EHEC IgG and sIgA in sera and feces. HP candidate-immunized mice displayed elevated levels of Th2 cytokines and diminished cecum colonization after wild-type challenge. Individually tested HP vaccine candidates showed that pVAX-12 and pVAX-56.2 significantly induced Th2 cytokines and production of fecal EHEC sIgA, with pVAX-56.2 reducing EHEC cecum colonization. We describe here a bioinformatics approach able to identify novel vaccine candidates potentially useful for preventing EHEC O157:H7 infections.

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“…For the development of an effective vaccine against EHEC-related pathogenicity [16], [17], STxB subunit-based immunogens that have ability to induce anti-Shiga toxin antibodies have been investigated by several laboratories [18]–[20]. However, no vaccine able to prevent EHEC infection and/or STx-mediated HUS for humans and animals has been reported [18], [21].…”

Section: Discussionmentioning

confidence: 99%

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

Choi

Kim

et al. 2014

PLoS ONE

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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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Subcutaneous and intranasal immunization with Stx2B–Tir–Stx1B–Zot reduces colonization and shedding of Escherichia coli O157:H7 in mice

Cited by 32 publications

References 29 publications

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Comparative Genomics and Immunoinformatics Approach for the Identification of Vaccine Candidates for Enterohemorrhagic Escherichia coli O157:H7

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

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