Vaccine-induced human antibodies to PspA augment complement C3 deposition on Streptococcus pneumoniae

Vaccine-induced human antibodies to PspA augment complement C3 deposition on Streptococcus pneumoniae
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DOI:
10.1016/j.micpath.2007.09.007
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发表时间:
2008-03-01
影响因子:
3.8
通讯作者:
Millar, Amanda
Millar, Amanda
中科院分区:
医学3区
文献类型:
--
作者:
Ochs, Martina M.;Bartlett, William;Millar, Amanda

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肺炎球菌表面蛋白(PspA)是由肺炎链球菌的所有临床分离株表达的毒力因子。PspA在结构上是可变的,并且已经基于序列相似性和免疫交叉反应性被分组为进化枝和交叉反应家族。至少98%的PspA存在于PspA家族I或2中。PspA已显示干扰肺炎球菌上的补体沉积,从而减少宿主免疫系统对细菌的调理作用和清除。先前使用合并的人血清的研究表明,PspA干扰C3在单一S菌株上的沉积。PspA的小鼠抗体可以增强C3在WU 2上的沉积。目前的研究表明,这些先前的发现代表了大多数正常人血清和七种不同的S.肺炎。据观察,PspA家族I和2的PspA可以抑制C3沉积的免疫球蛋白的存在下,除了3的22个正常人血清中存在。这些研究还表明,兔和人的抗体PspA可以增强沉积的C3的肺炎球菌表达家族I或2 PspA和任何荚膜类型2 - 3,或11。一种能引起中和或补偿沙门氏菌的免疫力的候选疫苗。pneumoniae的破坏宿主免疫的能力将是有价值的。(C)2007爱思唯尔有限公司保留所有权利。
Pneumococcal surface protein (PspA) is a virulence factor expressed by all clinical isolates of Streptococcus pneumoniae. PspAs are variable in structure and have been grouped into clades and cross-reacting families based on sequence similarities and immunologic cross-reactivity. At least 98%, of PspAs are found in PspA families I or 2. PspA has been shown to interfere with complement deposition on pneumococci, thus reducing opsonization and clearance of bacteria by the host immune system. Prior studies using pooled human sera have shown that PspA interferes with C3 deposition on a single strain of S. pneumoniae, WU2, and that mouse antibody to PspA can enhance the deposition of C3 on WU2. The present Studies have demonstrated that these previous findings are representative of most normal human sera and each of seven different strains of S. pneumoniae. It was observed that PspAs of PspA families I and 2 could inhibit C3 deposition in the presence of immunoglobulin present in all but 3 of 22 normal human sera. These studies have also demonstrated that rabbit and human antibody to PspA can enhance the deposition of C3 on pneumococci expressing either family I or 2 PspAs and either capsular types 2 3, or 11. A vaccine candidate that can elicit immunity that neutralizes or compensates for S. pneumoniae's ability to thwart host immunity would be of value. (C) 2007 Elsevier Ltd. All rights reserved.