The capsule of Streptococcus equi ssp. zooepidemicus is a target for attenuation in vaccine development.
The capsule of Streptococcus equi ssp. zooepidemicus is a target for attenuation in vaccine development.
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DOI：
10.1016/j.vaccine.2012.04.092
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发表时间：
2012-06
期刊：
影响因子：
5.5
通讯作者：
Zigong Wei;Qiang Fu;Yaosheng Chen;P. Cong;S. Xiao;Delin Mo;Zhuyong He;Xiaohong Liu
中科院分区：
文献类型：
--
作者：
Zigong Wei;Qiang Fu;Yaosheng Chen;P. Cong;S. Xiao;Delin Mo;Zhuyong He;Xiaohong Liu
马链球菌亚种动物寄生虫（Zoopellicus，SEZ）是一种重要的病原体，与许多哺乳动物的多种疾病有关。因此，研制新型有效疫苗将有助于控制SEZ感染。在本研究中，SEZ胶囊的重要性进行了检查，使用一个新构建的胶囊缺陷突变ΔhasB菌株。透射电子显微镜证实了突变体SEZ上细胞外荚膜多糖丰度的减少。与亲本野生型SEZ相比，ΔhasB突变体在小鼠中高度减毒，并且当作为活疫苗施用时提供100%的针对致死性攻击的保护。实时荧光定量PCR分析显示，免疫小鼠IL-4和IFN-γ mRNA水平明显升高。胶囊在SEZ致病性中所起的作用也在减毒疫苗靶标的机制设计方面进行了探索。该胶囊可以抵抗补体C3在SEZ细胞表面的沉积，并有助于防止补体介导的调理作用和培养的巨噬细胞的吞噬作用。这些结果表明，SEZ的荚膜在致病性中起重要作用，并可作为疫苗开发的减毒靶点。
Streptococcus equi ssp. zooepidemicus (SEZ) is an important pathogen associated with a wide range of diseases in many mammalian species. The development of novel effective vaccines would be beneficial to control SEZ infection. In the present study, the importance of the SEZ capsule was examined using a newly constructed capsule-deficient mutant ΔhasB strain. Transmission electron microscopy confirmed a decrease in the abundance of extracellular capsular polysaccharide on the mutant SEZ. Compared to the parental wild-type SEZ, the ΔhasB mutant was highly attenuated in mice and provided 100% protection against lethal challenge when administered as a live vaccine. Real-time PCR analysis showed a marked increased in the levels of IL-4 and IFN-γ mRNA in immunized mice. The role that the capsule plays in SEZ pathogenicity was also explored with respect to the mechanistic design of an attenuated vaccine target. The capsule could resist complement C3 deposition on the surface of SEZ cells and aid in preventing complement-mediated opsonization and phagocytosis by cultured macrophages. These results suggest that the capsule of SEZ plays an important role in pathogenicity and may serve as a target for attenuation in vaccine development.