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用链球菌多表位重组蛋白进行免疫可保护小鼠免受A组链球菌侵袭性感染。

Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection.

作者信息

Kuo Chih-Feng, Tsao Nina, Hsieh I-Chen, Lin Yee-Shin, Wu Jiunn-Jong, Hung Yu-Ting

机构信息

Department of Nursing, College of Medicine, I-Shou University, Kaohsiung, Taiwan.

Department of Biological Science and Technology, College of Medicine, I-Shou University, Kaohsiung, Taiwan.

出版信息

PLoS One. 2017 Mar 29;12(3):e0174464. doi: 10.1371/journal.pone.0174464. eCollection 2017.

Abstract

Streptococcus pyogenes (group A Streptococcus; GAS) causes clinical diseases, including pharyngitis, scarlet fever, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. A number of group A streptococcus vaccine candidates have been developed, but only one 26-valent recombinant M protein vaccine has entered clinical trials. Differing from the design of a 26-valent recombinant M protein vaccine, we provide here a vaccination using the polyvalence epitope recombinant FSBM protein (rFSBM), which contains four different epitopes, including the fibronectin-binding repeats domain of streptococcal fibronectin binding protein Sfb1, the C-terminal immunogenic segment of streptolysin S, the C3-binding motif of streptococcal pyrogenic exotoxin B, and the C-terminal conserved segment of M protein. Vaccination with the rFSBM protein successfully prevented mortality and skin lesions caused by several emm strains of GAS infection. Anti-FSBM antibodies collected from the rFSBM-immunized mice were able to opsonize at least six emm strains and can neutralize the hemolytic activity of streptolysin S. Furthermore, the internalization of GAS into nonphagocytic cells is also reduced by anti-FSBM serum. These findings suggest that rFSBM can be applied as a vaccine candidate to prevent different emm strains of GAS infection.

摘要

化脓性链球菌(A 组链球菌;GAS)可引发多种临床疾病,包括咽炎、猩红热、脓疱病、坏死性筋膜炎和链球菌中毒性休克综合征。目前已研发出多种 A 组链球菌候选疫苗,但仅有一款 26 价重组 M 蛋白疫苗进入了临床试验阶段。与 26 价重组 M 蛋白疫苗的设计不同,我们在此提供一种使用多价表位重组 FSBM 蛋白(rFSBM)的疫苗接种方法,该蛋白包含四个不同表位,分别是链球菌纤连蛋白结合蛋白 Sfb1 的纤连蛋白结合重复结构域、链球菌溶血素 S 的 C 末端免疫原性片段、链球菌致热外毒素 B 的 C3 结合基序以及 M 蛋白的 C 末端保守片段。用 rFSBM 蛋白进行疫苗接种成功预防了由多种 GAS emm 菌株感染引起的死亡和皮肤损伤。从接种 rFSBM 的小鼠体内收集的抗 FSBM 抗体能够调理至少六种 emm 菌株,并可中和链球菌溶血素 S 的溶血活性。此外,抗 FSBM 血清还能减少 GAS 进入非吞噬细胞的内化作用。这些研究结果表明,rFSBM 可作为一种候选疫苗用于预防不同 emm 菌株的 GAS 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b493/5371370/e28e9c5c3924/pone.0174464.g001.jpg

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