Development of a bivalent food poisoning vaccine: augmented antigenicity of the C-terminus of Clostridium perfringens enterotoxin by fusion with the B subunit of Escherichia coli Shiga toxin 2. (16th October 2018)

• Record Type: Journal Article
• Authors: Hosomi, Koji; Hinenoya, Atsushi; Suzuki, Hidehiko; Nagatake, Takahiro; Nishino, Tomomi; Tojima, Yoko; Hirata, So-ichiro; Matsunaga, Ayu; Kondoh, Masuo; Yamasaki, Shinji; Kunisawa, Jun
• Is Part Of: International immunology. Volume 31:Number 2(2019)
• Page Start: 91
• Page End: 100
• Publication Date: 2018-10-16
• Subjects: bacterial infection -- diarrhea -- hyperkalemia -- hemolytic uremic syndrome (HUS) -- T cell response; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxy071
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : A bivalent vaccine blocks two bacterial toxins that cause food poisoning Abstract: Food poisonings caused by Clostridium perfringens and Shiga toxin (Stx)-producing Escherichia coli (STEC) occur frequently worldwide; however, no vaccine is currently available. Therefore, we aimed to develop a bivalent vaccine against C. perfringens and STEC infections. Although it has been considered that the C-terminal region of C. perfringens enterotoxin (C-CPE) could be a good vaccine antigen to block the binding to its receptor, it was insufficient for induction of a protective immune response because of the low antigenicity. However, the fusion of C-CPE with Stx2 B subunit (Stx2B) augmented the antigenicity of C-CPE without affecting the antigenicity of Stx2B. Indeed, high levels of C-CPE-specific neutralizing IgG were found in the serum of mice immunized with the fusion protein Stx2B–C-CPE. Additionally, comparable and substantial levels of Stx2B-specific neutralizing IgG were induced in mice receiving Stx2B–C-CPE or Stx2B alone. These antibody responses against C-CPE and Stx2B lasted for at least 48 weeks, which were sufficient for protective immunity in vitro and in vivo, indicating that Stx2B–C-CPE could induce long-term protective immunity. As an underlying mechanism, ex vivo stimulation with Stx2B, but not with C-CPE, induced cytokine production from splenic T cells collected from mice immunized with Stx2B–C-CPE, suggesting that Stx2B-specific, but not C-CPE-specific, T cells were induced by the immunization with Stx2B–C-CPE and plausibly promoted immunoglobulin class switching of both Stx2B- and C-CPE-specific B cells from IgM to IgG. These findings collectively indicate that Stx2B–C-CPE is a T-cell-antigen-supplement-type bivalent vaccine, which could be an efficient against C. perfringens and STEC infections.