Pneumococcal surface protein A is expressed in vivo, and antibodies to PspA are effective for therapy in a murine model of pneumococcal sepsis.
Pneumococcal surface protein A is expressed in vivo, and antibodies to PspA are effective for therapy in a murine model of pneumococcal sepsis.
复制标题
肺炎球菌表面蛋白 A 在体内表达，PspA 抗体可有效治疗肺炎球菌脓毒症小鼠模型。
DOI：
10.1128/iai.71.12.7149-7153.2003
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发表时间：
2003
影响因子：
3.1
通讯作者：
Briles,DE
中科院分区：
文献类型：
--
作者：
Swiatlo,E;King,J;Nabors,GS;Mathews,B;Briles,DE
肺炎球菌表面蛋白A(PSPA)是一种免疫原性蛋白，表达于所有肺炎链球菌(肺炎球菌)的表面，能诱导小鼠产生抗体，保护小鼠免受侵袭性感染。在保护性研究中用于感染挑战的肺炎球菌通常是从体外半合成培养基中收集的。这些研究的目的是证实肺炎球菌在体内生长过程中表达PSPA，其水平足以使PSPA的抗体起到保护作用。用纯化的PSPA或通过被动转移单抗(MAb)主动免疫小鼠，并用菌血症小鼠稀释的全血中的3型衣壳毒株攻击。所有小鼠都受到10倍50%致死剂量(LD50)的攻击保护，与对照组相比，受到1000倍LD50攻击的小鼠存活率有所提高。此外，在感染后6h和12h，用10倍LD50的PSPA单抗或PSPA免疫血清处理非免疫小鼠，也能提高小鼠的存活率。对体外和体内培养的肺炎球菌的RNA进行Northern印迹分析，结果显示PSPA的mRNA水平相似。这些结果表明PSPA在小鼠模型中是活体表达的，并且PSPA免疫诱导了对侵袭性感染过程中表达的抗原的抗体。使用PSPA抗体的免疫疗法在治疗人类肺炎球菌感染方面可能有一定的实用价值。
Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains ofStreptococcus pneumoniae(pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at a level sufficient for antibodies to PspA to be protective. Mice were actively immunized with purified PspA or by passive transfer of monoclonal antibody (MAb) and challenged with a capsular type 3 strain in diluted whole blood from bacteremic mice. All were protected against challenge with 10 times the 50% lethal dose (LD50), and mice challenged with 1,000 times the LD50had increased survival compared with controls. Additionally, nonimmune mice treated with MAbs to PspA or PspA immune serum at 6 and 12 h after infection with 10 times the LD50also showed increased survival. Northern blot analysis of RNA from pneumococci grown either in vitro or in vivo showed similar levels of PspA mRNA. These results demonstrate that PspA is expressed in vivo in a mouse model and that immunization with PspA induces antibodies to an antigen which is expressed during the course of invasive infection. Immunotherapy with antibodies to PspA may have some utility in treating pneumococcal infections in humans.