A multi-epitope fusion antigen candidate vaccine for Enterotoxigenic Escherichia coli is protective against strain B7A colonization in a rabbit model.

Richard M Jones,Weiping Zhang,David A Sack,Hyesuk Seo,Alfredo G Torres

doi:10.1371/journal.pntd.0010177

Abstract

Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children’s and travelers’ diarrhea. Developing effective vaccines against this heterologous group has proven difficult due to the varied nature of toxins and adhesins that determine their pathology. A multivalent candidate vaccine was developed using a multi-epitope fusion antigen (MEFA) vaccinology platform and shown to effectively elicit broad protective antibody responses in mice and pigs. However, direct protection against ETEC colonization of the small intestine was not measured in these systems. Colonization of ETEC strains is known to be a determining factor in disease outcomes and is adhesin-dependent. In this study, we developed a non-surgical rabbit colonization model to study immune protection against ETEC colonization in rabbits. We tested the ability for the MEFA-based vaccine adhesin antigen, in combination with dmLT adjuvant, to induce broad immune responses and to protect from ETEC colonization of the rabbit small intestine. Our results indicate that the candidate vaccine MEFA antigen elicits antibodies in rabbits that react to seven adhesins included in its construction and protects against colonization of a challenge strain that consistently colonized naïve rabbits.

Highlights

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of children’s and travelers’ diarrhea across the globe [1]
We have developed a single protein vaccine candidate called a multi-epitope fusion antigen (MEFA) that elicits antibody production in mice and pigs against seven diverse colonization factors
We took advantage of a rabbit model of ETEC colonization to determine if immunization with this MEFA can provide direct protection against colonization of the small intestine

Summary

Introduction

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of children’s and travelers’ diarrhea across the globe [1]. More pressing, these strains are a leading cause of death in children under 5 years old in developing country settings [2,3,4]. ETEC strains are characterized by the presence of enterotoxins and adhesins. In addition to the expression of these toxins, ETEC strains utilize a large number of immunologically heterologous adhesins known as colonization factor antigens (CFA) [5]. Attachment and adherence by ETEC adhesins to host receptors allow for colonization of the organism in the host small intestine, eventually leading to establishment of infection

Methods

Results

Discussion

Conclusion