Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, China.
Vet Res. 2021 Jun 2;52(1):75. doi: 10.1186/s13567-021-00939-5.
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.
布鲁氏菌属是革兰氏阴性、兼性细胞内细菌，可引起人类和各种动物的布鲁氏菌病。布鲁氏菌病的威胁日益增加，但目前可用的活减毒疫苗仍存在缺陷。因此，迫切需要使用蛋白抗原制备的亚单位疫苗，这种疫苗具有安全、经济有效和有效的优势。在本研究中，我们使用核心蛋白质组分析和综合 RV 方法，从全球地理分布的 213 株致病性布鲁氏菌属菌株中筛选针对广谱抗原的潜在候选物。候选蛋白根据六个生物学特征进行评分：亚细胞定位、抗原相似性、抗原性、成熟表位密度、毒力和黏附概率。在 RV 分析中，总共挑选出 32 种候选抗原。其中，三种蛋白被选择用于评估免疫原性和初步保护作用：外膜蛋白 Omp19（用作阳性对照）、IV 型分泌系统（T4SS）蛋白 VirB8 和 I 型分泌系统（T1SS）蛋白 HlyD。这三种具有高度保守性的蛋白能够诱导特异性体液和细胞免疫反应。Omp19、VirB8 和 HlyD 可显著降低小鼠中 B.abortus S19 的器官细菌载量，并提供不同程度的保护。在本研究中，我们证明了这种独特策略用于筛选针对布鲁氏菌的潜在广谱抗原的有效性。需要进一步评估疫苗抗原对野生型致病性布鲁氏菌属菌株攻击的保护水平。
