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
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
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开发二价食物中毒疫苗：通过与大肠杆菌志贺毒素 2 的 B 亚基融合，增强产气荚膜梭菌肠毒素 C 末端的抗原性
DOI：
10.1093/intimm/dxy071
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发表时间：
2018
影响因子：
4.4
通讯作者：
Kunisawa Jun
中科院分区：
文献类型：
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作者：
Hosomi Koji;Hinenoya Atsushi;Suzuki Hidehiko;Nagatake Takahiro;Nishino Tomomi;Tojima Yoko;Hirata So-ichiro;Matsunaga Ayu;Kondoh Masuo;Yamasaki Shinji;Kunisawa Jun
产气荚膜梭菌和产滋贺毒素大肠杆菌引起的食物中毒在世界范围内频繁发生，然而，目前还没有疫苗可用。因此，我们的目标是开发针对C的双价疫苗。产气荚膜杆菌和STEC感染。尽管人们一直认为C.产气荚膜梭菌毒素（C-CPE）是一种很好的疫苗抗原，可阻断其与受体的结合，但其抗原性较低，不足以诱导保护性免疫应答。C-CPE与Stx 2 B亚基（Stx 2 B）的融合增强了C-CPE的抗原性，但不影响Stx 2 B的抗原性。实际上，在用融合蛋白Stx 2B-C-CPE免疫的小鼠的血清中发现高水平的C-CPE特异性中和IgG。此外，在接受Stx 2B-C-CPE或单独Stx 2B的小鼠中诱导了相当和实质水平的Stx 2B特异性中和IgG。这些针对C-CPE和Stx 2B的抗体反应持续至少48周，足以在体外和体内产生保护性免疫，表明Stx 2B-C-CPE可以诱导长期保护性免疫。作为潜在机制，用Stx 2 B而不是C-CPE的离体刺激诱导从用Stx 2 B-C-CPE免疫的小鼠收集的脾T细胞产生细胞因子，表明Stx 2 B特异性而不是C-CPE特异性T细胞通过用Stx 2 B-C-CPE免疫诱导，并且可促进Stx 2 B和C-CPE特异性B细胞从IgM到IgG的免疫球蛋白类别转换。这些结果共同表明，Stx 2B-C-CPE是一种T细胞抗原补充型双价疫苗，可能是一种有效的抗C。产气荚膜杆菌和STEC感染。
Food poisonings caused byClostridium perfringensand Shiga toxin (Stx)-producingEscherichia coli(STEC) occur frequently worldwide; however, no vaccine is currently available. Therefore, we aimed to develop a bivalent vaccine againstC. perfringensand STEC infections. Although it has been considered that the C-terminal region ofC. perfringensenterotoxin (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 immunityin vitroandin vivo, indicating that Stx2B–C-CPE could induce long-term protective immunity. As an underlying mechanism,ex vivostimulation 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 againstC. perfringensand STEC infections.