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

David A Montero,Ángel Oñate,Roberto M Vidal,Mauricio Arenas-Salinas,Felipe Del Canto,José Reyes,Juan C Salazar,Sandra Céspedes,Leandro Cádiz

doi:10.1038/s41541-020-0168-7

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.

Highlights

Shiga toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens causing acute and bloody diarrhea, which may progress to life-threatening complications such as hemolytic uremic syndrome (HUS)[1]
Outer membrane protease T (OmpT), Calcium binding antigen homolog (Cah) and Hemagglutinin from STEC (Hes) proteins induces immune responses that reduce intestinal colonization and prevent renal damage caused by STEC
Sera obtained from Chilean-hospitalized pediatric patients diagnosed with HUS, after STEC primoinfection, recognizes antigens such as OmpT, Cah and Hes, as a result of a primary immune response to an initial STEC antigen exposure with the development of immunological memory[13]

Summary

Introduction

Shiga toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens causing acute and bloody diarrhea, which may progress to life-threatening complications such as hemolytic uremic syndrome (HUS)[1]. To date there is no specific treatment for STEC infection and antibiotic use is contraindicated due to increased risk of HUS development[2]. STEC colonizes the human colon and produces Shiga toxins (Stx) that can enter the blood stream and disseminate to organs such as the kidneys and central nervous system. Once Stx reach the target organs and enter the cells, the toxins inhibit protein synthesis, leading to autophagy and apoptosis and tissue damage, which may lead to HUS7

Methods

Results

Conclusion