Abstract

Clostridium perfringens enterotoxin (CPE) is a common cause of food poisoning and hyperkalemia-associated death. Previously, we reported that fusion of pneumococcal surface protein A (PspA) to C-terminal fragment of CPE (C-CPE) efficiently bound mucosal epithelium so that PspA-specific immune responses could be provoked. In this study, we found that fusion of C-CPE with PspA augmented the antigenicity of C-CPE itself. These findings allowed us to hypothesize that fusion of C-CPE and another food poisoning vaccine act as a bivalent food poisoning vaccine. Therefore, we constructed an adjuvant-free bivalent vaccine against CPE and cholera toxin (CT), which is a major food poisoning in developing country, by genetically fusing CT B subunit to C-CPE. Because of the low antigenicity of C-CPE, immunization of mice with C-CPE alone did not induce C-CPE-specific immune responses. However, immunization with our vaccine induced both C-CPE- and CT-specific neutralizing antibody. The underlying mechanism of the augmented antigenicity of C-CPE included the activation of T cells by CTB. Moreover, neutralizing antibodies lasted for at least 48 weeks and the quality of the antibody was dependent on the binding activity of CTB–C-CPE to its receptors. These findings suggest that our fusion protein is a potential platform for the development of an adjuvant-free bivalent vaccine against CPE and CT.

Highlights

  • Food poisoning is caused by intake of food or water contaminated with pathogens such as bacteria, viruses, parasites, and toxins

  • We previously reported that C-Clostridium perfringens enterotoxin (CPE) was a useful vehicle for the delivery of a genetically fused antigen [i.e., pneumococcal surface protein A (PspA)] to the mucosal epithelium to induce antigenspecific immune responses without the need for an adjuvant [19, 20]

  • We found that serum from mice immunized with CTB–C-terminal fragment of CPE (C-CPE) inhibited the binding of CTB–C-CPE to claudin-4 (Figure S7)

Read more

Summary

Introduction

Food poisoning is caused by intake of food or water contaminated with pathogens such as bacteria, viruses, parasites, and toxins. The World Health Organization estimates that each year 600 million people worldwide contract food poisoning and 420,000 people die from food poisoning-associated causes [1]. Clostridium perfringens is a spore-forming bacterium distributed in soil, sewage, and food, and in animals and humans, that is a frequent cause of food poisoning (>4 million cases worldwide/year) and occasionally death [3]. C. perfringensassociated food poisoning causes an estimated economic burden of $382 million per year in the US [4]. C. perfringens type A produces CPE, and the symptoms of food poisoning associated with ingestion of CPE develop 8 to 18 h after intake of contaminated food [6]. A vaccine against C. perfringens-associated food poisoning is needed

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call