Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producing Escherichia coli

Abstract

Shiga toxin-producing Escherichia coli (STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7, the intranasal conferred protection against renal damage caused by STEC O91:H21. This preclinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.

GlnH, a Novel Antigen That Offers Partial Protection against Verocytotoxigenic Escherichia coli Infection

“…This oral challenge model with the monitoring of faecal shedding and gastrointestinal colonisation represents a safe and useful VTEC colonisation model in the absence of BLS3 animal facilities. Murine VTEC colonisation models are cost-effective models that are feasible for large sample sizes and have been used previously for VTEC vaccine testing [ 29 , 69 , 70 ], but they have limitations, as they are not naturally colonised by VTEC strains and thus do not develop symptoms [ 16 , 32 ]. Consequently, persistent levels of colonisation are not maintained after 7 days.…”

Embedding of exogenous B cell epitopes on the surface of UreB structure generates a broadly reactive antibody response against Helicobacter pylori

“…It is possible to correlate the protection achieved with high levels of H. pylori-specific IgG (Figure 6b). Some studies revealed that IgG antibodies lead to the elimination of the Shiga toxin-producing Escherichia coli, virulent Citrobacter rodentium, and rotavirus in the murine intestine [32,48,49]. The vaccines against H. pylori were also vaccinated by systemic immune routes such as intramuscular immunisation [50,51].…”

“…The engineered immunogens could present one or more key epitopes or immunogenic domains to induce epitope-specific antibodies or generate a broadly reactive antibody response. In recent studies, Roundleaf bat HBV core antigen, calcium-binding antigen 43 homologue (Cah), and H. pylori ferritin were respectively selected as the scaffold proteins for displaying key epitopes or immunogenic domains of pathogens including hepatitis B virus, Shiga toxin-producing Escherichia coli (E. coli) and Borrelia burgdorferi [31][32][33]. The structure-based engineered immunogen has higher structural stability and more reasonable epitope exposure compared to epitope-tandem immunogens, which means that it could generate a broader and more persistent antibody response.…”

A chimeric protein-based vaccine elicits a strong IgG antibody response and confers partial protection against Shiga toxin-producing Escherichia coli in mice

“…In addition to these conventional antigens, there is growing interest in exploring alternative vaccine approaches that target non-LEEencoded antigens. For instance, the subunit B of the Shiga toxin 2 (Stx2B), and outer membrane proteins such as LomW, OmpT, Cah and Hes have gained attention as potential antigens for vaccine development (20,22,(25)(26)(27)(28)(29).…”

“…One promising strategy is the use of chimeric proteins that carry selected epitopes from various strains or pathogens. This approach has shown the potential to enhance the immunogenicity of the recombinant antigen and the possibility of eliciting a broader immune response ( 28 , 32 , 39 ).…”