Huang Jing, Pan Chao, Sun Peng, Feng Erling, Wu Jun, Zhu Li, Wang Hengliang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai, Beijing 100071, China.
Microorganisms. 2020 Mar 20;8(3):436. doi: 10.3390/microorganisms8030436.
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. - and -linked glycosylation systems have been successfully developed and exploited for the production of successful bioconjugate vaccines. Here, we applied an -linked glycosylation system to a low-pathogenicity bacterium, serotype O:9 ( O:9), which has repeating units of O-antigen polysaccharide (OPS) identical to that of (), to develop a bioconjugate vaccine against . The glycoprotein we produced was recognized by both anti- and anti- O:9 monoclonal antibodies. Three doses of bioconjugate vaccine-elicited OPS-specific serum IgG in mice, significantly reducing bacterial loads in the spleen following infection with the hypovirulent smooth strain A19. This candidate vaccine mitigated 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 .
布鲁氏菌病是一种全球性的主要人畜共患公共卫生威胁，在流行地区会导致兽医发病率和重大经济损失。然而，目前尚无有效的布鲁氏菌病疫苗，动物常用的减毒活疫苗可导致人类感染。N-连接糖基化系统已成功开发并用于生产成功的生物共轭疫苗。在此，我们将N-连接糖基化系统应用于低致病性细菌牛种布鲁氏菌O:9血清型（B. abortus O:9），其O抗原多糖（OPS）的重复单元与羊种布鲁氏菌（B. melitensis）相同，以开发一种抗羊种布鲁氏菌的生物共轭疫苗。我们生产的糖蛋白可被抗羊种布鲁氏菌和抗牛种布鲁氏菌O:9单克隆抗体识别。三剂生物共轭疫苗在小鼠中引发了羊种布鲁氏菌OPS特异性血清IgG，在用低毒力光滑菌株A19感染后显著降低了脾脏中的细菌载量。这种候选疫苗减轻了羊种布鲁氏菌感染并预防了严重的组织损伤，从而抵御了A19的致死性攻击。总体而言，结果表明该生物共轭疫苗引发了强烈的免疫反应，并为布鲁氏菌病提供了显著的保护作用。所描述的疫苗制备策略是安全的，并且避免了高致病性羊种布鲁氏菌的大规模培养。
