Application of an O-Linked Glycosylation System in Yersinia enterocolitica Serotype O:9 to Generate a New Candidate Vaccine against Brucella abortus
Application of an O-Linked Glycosylation System in Yersinia enterocolitica Serotype O:9 to Generate a New Candidate Vaccine against Brucella abortus
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应用 O 联糖基化系统在小肠结肠炎耶尔森氏菌 O:9 血清型中生成抗流产布鲁氏菌的新候选疫苗。
DOI：
10.3390/microorganisms8030436
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发表时间：
2020-03-01
期刊：
影响因子：
4.5
通讯作者：
Wang, Hengliang
中科院分区：
文献类型：
--
作者：
Huang, Jing;Pan, Chao;Wang, Hengliang
布鲁氏菌病是一种主要的人畜共患公共卫生威胁，在流行地区造成兽医发病率和重大经济损失。然而，目前还没有有效的布鲁氏菌病疫苗，通常用于动物的减毒活疫苗可引起人类感染。N-和0-连接的糖基化系统已被成功开发并用于生产成功的生物缀合物疫苗。在这里，我们将O-连接的糖基化系统应用于低致病性细菌，小肠结肠炎耶尔森氏菌血清型O：9（Y。小肠结肠炎菌O：9），其具有与流产布鲁氏菌（B.牛种布鲁氏菌），以开发针对布鲁氏菌的生物缀合物疫苗。所制备的糖蛋白能被抗B.流产和抗Y.小肠结肠炎O：9单克隆抗体。三剂生物结合物疫苗诱发B。牛胎OPS特异性血清IgG，显著降低B感染后脾脏中的细菌负荷。牛流产杆菌弱毒力光滑菌株A19。该候选疫苗缓解了B。流产感染，并防止严重的组织损伤，从而保护免受致命的挑战与A19。总体而言，结果表明，生物结合物疫苗引起了强烈的免疫应答，并提供了针对布鲁氏菌病的显著保护。所描述的疫苗制备策略是安全的，并且避免了高致病性B的大规模培养。流产
Brucellosis is a major zoonotic public health threat worldwide, causing veterinary morbidity and major economic losses in endemic regions. However, no efficacious brucellosis vaccine is yet available, and live attenuated vaccines commonly used in animals can cause human infection. N- and O-linked glycosylation systems have been successfully developed and exploited for the production of successful bioconjugate vaccines. Here, we applied an O-linked glycosylation system to a low-pathogenicity bacterium, Yersinia enterocolitica serotype O:9 (Y. enterocolitica O:9), which has repeating units of O-antigen polysaccharide (OPS) identical to that of Brucella abortus (B. abortus), to develop a bioconjugate vaccine against Brucella. The glycoprotein we produced was recognized by both anti-B. abortus and anti-Y. enterocolitica O:9 monoclonal antibodies. Three doses of bioconjugate vaccine-elicited B. abortus OPS-specific serum IgG in mice, significantly reducing bacterial loads in the spleen following infection with the B. abortus hypovirulent smooth strain A19. This candidate vaccine mitigated B. abortus infection and prevented severe tissue damage, thereby protecting against lethal challenge with A19. Overall, the results indicated that the bioconjugate vaccine elicited a strong immune response and provided significant protection against brucellosis. The described vaccine preparation strategy is safe and avoids large-scale culture of the highly pathogenic B. abortus.