Development of Adjuvant-Free Bivalent Food Poisoning Vaccine by Augmenting the Antigenicity of Clostridium perfringens Enterotoxin.

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.

• Authors: Hidehiko Suzuki, Koji Hosomi, Ayaka Nasu, Masuo Kondoh, Jun Kunisawa
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 2320 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30356722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antibodies, Neutralizing
• Bacterial Vaccines
• Enterotoxins
• enterotoxin, Clostridium

Topics

• Animals
• Antibodies, Bacterial (immunology)
• Antibodies, Neutralizing (immunology)
• Antibody Specificity (immunology)
• Bacterial Vaccines (administration & dosage, genetics, immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Clostridium Infections (immunology, prevention & control)
• Clostridium perfringens (genetics, immunology)
• Disease Models, Animal
• Enterotoxins (administration & dosage, genetics, immunology)
• Female
• Foodborne Diseases (immunology, prevention & control)
• Host-Pathogen Interactions (immunology)
• Immunization
• Immunogenicity, Vaccine
• Intestinal Mucosa (immunology, metabolism, pathology)
• Mice
• Neutralization Tests
• T-Cell Antigen Receptor Specificity (immunology)