Zhang Xinyu, Yu Shupei, Cheng Darong, Feng Yu, Yang Yuefei, Sun Huaichang, Ding Jiabo, Wang Fang
College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Front Vet Sci. 2021 Feb 12;7:620255. doi: 10.3389/fvets.2020.620255. eCollection 2020.
To develop an attenuated vaccine candidate against K88ac enterotoxigenic (ETEC), a novel () K88ac Δ with mutation and deletion was generated using site mutagenesis and λ-Red homologous recombination based on wild paternal ETEC strain C83902. K88ac Δ showed very similar fimbriae expression and growth kinetics to the wild strain C83902, but it was significantly attenuated according to the results of a rabbit ligated ileal loop assay and mouse infection study. Oral inoculation with K88ac Δ stimulated the mucosa immune response and induced the secretion of IgA to K88ac in the intestines in mice. A challenge experiment revealed that the attenuated strain provided efficient protection against C83902 in the following 7 days and at the 24th day post-inoculation, suggesting that the attenuated isolate could act as an ecological protectant and vaccine in preventing K88ac ETEC.
为开发一种针对K88ac产肠毒素大肠杆菌(ETEC)的减毒疫苗候选株,基于野生亲本ETEC菌株C83902,利用定点诱变和λ-Red同源重组技术构建了一种新型的带有突变和缺失的K88ac Δ。K88ac Δ与野生菌株C83902表现出非常相似的菌毛表达和生长动力学,但根据兔肠结扎环试验和小鼠感染研究结果,其毒力显著减弱。用K88ac Δ口服接种可刺激小鼠黏膜免疫反应并诱导肠道中针对K88ac的IgA分泌。攻毒实验表明,该减毒株在接种后第7天和第24天能有效保护小鼠免受C83902感染,这表明该减毒分离株可作为一种生态保护剂和疫苗来预防K88ac ETEC。