Group A Streptococcus Cell Wall Oligosaccharide-Streptococcal C5a Peptidase Conjugates as Effective Antibacterial Vaccines.,ACS Infectious Diseases

当前位置： X-MOL 学术 › ACS Infect. Dis. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Group A Streptococcus Cell Wall Oligosaccharide-Streptococcal C5a Peptidase Conjugates as Effective Antibacterial Vaccines.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-01-07 , DOI: 10.1021/acsinfecdis.9b00347
Subo Wang ₁ , Yisheng Zhao ₁ , Guirong Wang ₁ , Shaojie Feng ₁ , Zhongwu Guo ₂ , Guofeng Gu ₁

Affiliation

Group A streptococcus (GAS) is one of the common Gram-positive pathogenic bacteria accounting for a variety of infectious diseases. Currently, there is no commercial vaccine for GAS. To develop efficient GAS vaccines, synthetic tri-, hexa-, and nonasaccharides of a conserved group A carbohydrate (GAC) were conjugated with an inactive mutant of group A streptococcal C5a peptidase (ScpA), ScpA193, to create bivalent conjugate vaccines, which were compared with the corresponding CRM197 and TT conjugates. Systematic evaluations of these semisynthetic conjugates demonstrated that they could induce robust and comparable T-cell-dependent immune responses in mice. It was further disclosed that antibodies provoked by the ScpA193 conjugates, especially that of hexa- and nonasaccharides, could recognize and bind to GAS cells and mediate GAS opsonophagocytosis in vitro. In vivo evaluations of the hexa- and nonasaccharide-ScpA193 conjugates using a mouse model revealed that immunizing mice with especially the latter conjugate could effectively protect the animals from GAS challenges and GAS-induced pulmonary damage and significantly increase animal survival. Further in vitro studies suggested that the two ScpA193 conjugates could function through activating CD4+ T cells and promoting helper T cells (Th) to differentiate into antigen-specific Th1 and Th2 cells. In conclusion, the nonasaccharide-ScpA193 conjugate was identified as a particularly promising GAS vaccine candidate that is worthy of further investigation and development.

中文翻译：

A组链球菌细胞壁寡糖-链球菌C5a肽酶可作为有效的抗菌疫苗。

A组链球菌（GAS）是引起多种传染病的常见革兰氏阳性病原菌之一。当前，没有用于GAS的商业疫苗。为了开发有效的GAS疫苗，将保守的A组碳水化合物（GAC）的合成三糖，六糖和九糖与A组链球菌C5a肽酶（ScpA）的失活突变体ScpA193偶联，以制备二价偶联疫苗，与相应的CRM197和TT共轭物进行比较。这些半合成缀合物的系统评价表明，它们可以在小鼠中诱导强大且可比的T细胞依赖性免疫应答。进一步公开了由ScpA193缀合物激发的抗体，特别是六糖和九糖的抗体，在体外可以识别并结合GAS细胞并介导GAS调理吞噬作用。使用小鼠模型对六糖和九糖-ScpA193缀合物进行的体内评估显示，尤其是用后者的缀合物免疫小鼠可以有效保护动物免受GAS攻击和GAS诱导的肺损伤，并显着提高动物存活率。进一步的体外研究表明，两种ScpA193偶联物可以通过激活CD4 + T细胞和促进辅助性T细胞（Th）分化为抗原特异性Th1和Th2细胞而发挥功能。总之，九糖-ScpA193偶联物被鉴定为特别有前途的GAS疫苗候选者，值得进一步研究和开发。使用小鼠模型对六糖和九糖-ScpA193偶联物进行的体内评估显示，尤其是后一种偶联物免疫小鼠可以有效保护动物免受GAS攻击和GAS诱导的肺损伤，并显着提高动物存活率。进一步的体外研究表明，两种ScpA193偶联物可以通过激活CD4 + T细胞和促进辅助性T细胞（Th）分化为抗原特异性Th1和Th2细胞而发挥功能。总之，九糖-ScpA193偶联物被鉴定为特别有前途的GAS疫苗候选者，值得进一步研究和开发。使用小鼠模型对六糖和九糖-ScpA193偶联物进行的体内评估显示，尤其是后一种偶联物免疫小鼠可以有效保护动物免受GAS攻击和GAS诱导的肺损伤，并显着提高动物存活率。进一步的体外研究表明，两种ScpA193偶联物可以通过激活CD4 + T细胞和促进辅助性T细胞（Th）分化为抗原特异性Th1和Th2细胞而发挥功能。总之，九糖-ScpA193偶联物被鉴定为特别有前途的GAS疫苗候选者，值得进一步研究和开发。

更新日期：2020-01-08

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11