Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.02320
Keywords
vaccine; food poisoning; Clostridium perfringens enterotoxin; cholera toxin; mucosal immunity
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science [JP17K08301, JP16H01373, JP15H05790, JP26293111, JP17H04134, JP17K09604, JP18H02150, JP18H02674, JP18J00556, JP18K17997, JP18K19400]
- Ministry of Health, Labour and Welfare of Japan
- Japan Agency for Medical Research and Development [JP18fk0108023h0003, JP18fk0108007h0003, JP18ek0410032s0103, JP18ck0106243h0003, JP18gm1010006h0002, JP18ak0101068h0002]
- Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry
- Institute of Medical Science, the University of Tokyo
- Terumo Foundation for Life Sciences and Arts
- ONO Medical Research Foundation
- Canon Foundation
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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.
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