Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection

Abstract

Enterohemorrhagic Escherichia coli (EHEC) strains are food borne pathogens with importance in public health. EHEC colonizes the large intestine and causes diarrhea, hemorrhagic colitis and in some cases, life-threatening hemolytic-uremic syndrome (HUS) due to the production of Shiga toxins (Stx). The lack of effective clinical treatment, sequelae after infection and mortality rate in humans supports the urgent need of prophylactic approaches, such as development of vaccines. Shedding from cattle, the main EHEC reservoir and considered the principal food contamination source, has prompted the development of licensed vaccines that reduce EHEC colonization in ruminants. Although murine models do not fully recapitulate human infection, they are commonly used to evaluate EHEC vaccines and the immune/protective responses elicited in the host. Mice susceptibility differs depending of the EHEC inoculums; therefore, displaying different mortality rates and Stx-mediated renal damage. Therefore, several experimental protocols have being pursued in this model to develop EHEC-specific vaccines. Recent candidate vaccines evaluated include those composed of virulence factors alone or as fused-subunits, DNA-based, attenuated bacteria and bacterial ghosts. In this review, we summarize progress in the design and testing of EHEC vaccines and the use of different strategies for the evaluation of novel EHEC vaccines in the murine model.

In silico analysis of Shiga toxins (Stxs) to identify new potential vaccine targets for Shiga toxin-producing Escherichia coli

“…Moreover, a number of studies aimed to evaluate the immunogenicity of the purified B subunit or its derivative, 2S protein. The results of the studies have been showed that the vaccines induced antibodies are able to neutralize the cytotoxic activity of both Stxs (Garcia-Angulo et al 2013).…”

“…Enterohaemorrhagic Escherichia coli (EHEC) strains are food-borne zoonotic pathogens that can cause of sporadic outbreaks, globally (Garcia-Angulo et al 2013). EHEC can cause severe gastroenteritis, hemorrhagic colitis and in some cases, Hemolytic uremic syndrome (HUS) due to the production of Shiga toxins (Stxs) (Basu and Tumer 2015).…”

“…Ruminants, especially cattle are considered as a reservoir for EHEC O157:H7 and fecal shedding leads to food contamination. Studies in cattle from high prevalence countries demonstrated carriage ranging from \1% to more than 30% (Garcia-Angulo et al 2013).…”

“…In addition, the essential virulence factor of EHEC, Stxs has been used for vaccination by induction of immunity responses to prevent intoxication. Primary studies demonstrated that vaccination with inactive Stx-derivatives could effectively induce the production of neutralizing antibodies and in some cases, induce protection against toxemia in animal models (Garcia-Angulo et al 2013). Moreover, a number of studies aimed to evaluate the immunogenicity of the purified B subunit or its derivative, 2S protein.…”

Exploiting the power of OMICS approaches to produceE. coliO157 vaccines

“…15 In support of our analysis, the HP group includes several proteins that we and others have previously identified as important virulence factors of EHEC O157:H7 as well as other proteins not previously identified in virulence but which were consider important immunogens. [18][19][20][21][22][23] Several studies in murine models of EHEC infection have emphasized the importance of mucosal delivery routes as a promising way to induce immune responses offering a combination of protection and blockage of EHEC intestinal colonization, mainly through expression of secretory IgA (sIgA) 24 (Fig. 1).…”