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脑膜炎奈瑟菌细胞表面LP2086的检测及其在B群荚膜多糖存在情况下的可及性

Detection of LP2086 on the cell surface of Neisseria meningitidis and its accessibility in the presence of serogroup B capsular polysaccharide.

作者信息

McNeil Lisa K, Murphy Ellen, Zhao Xiao-Juan, Guttmann Stephen, Harris Shannon L, Scott Adrienne A, Tan Cuiwen, Mack Michelle, DaSilva Ida, Alexander Kristin, Mason Kathryn, Jiang Han-Qing, Zhu Duzhang, Mininni Terri L, Zlotnick Gary W, Hoiseth Susan K, Jones Thomas R, Pride Michael W, Jansen Kathrin U, Anderson Annaliesa S

机构信息

Wyeth Research, 401 N. Middletown Rd., Pearl River, NY 10965, United States.

出版信息

Vaccine. 2009 May 26;27(25-26):3417-21. doi: 10.1016/j.vaccine.2009.01.075. Epub 2009 Feb 5.

DOI:10.1016/j.vaccine.2009.01.075
PMID:19200847
Abstract

The outer membrane protein LP2086, a human factor H binding protein, is undergoing clinical trials as a vaccine against invasive serogroup B meningococcal (MnB) disease. As LP2086 is a surface protein, expression of capsular polysaccharide could potentially limit accessibility of anti-LP2086 antibodies to LP2086 expressed on the surface of bacteria. To determine whether variability in expression levels of the serogroup B capsule (Cap B) might interfere with accessibility of anti-LP2086 antibody binding to LP2086, we evaluated the ability of anti-Cap B and anti-LP2086 antibodies to bind to the surface of 1263 invasive clinical MnB strains by flow cytometry. One of the anti-LP2086 monoclonal antibodies used recognizes virtually all LP2086 sequence variants. Our results show no correlation between the amount of Cap B expressed and the binding of anti-LP2086 antibodies. Furthermore, the susceptibility of MnB bacteria to lysis by anti-LP2086 immune sera was independent of the level of Cap B expressed. The data presented in this paper demonstrates that Cap B does not interfere with the binding of antibodies to LP2086 expressed on the outer membrane of MnB clinical isolates.

摘要

外膜蛋白LP2086是一种人源补体因子H结合蛋白,目前正作为抗B群侵袭性脑膜炎球菌(MnB)疾病的疫苗进行临床试验。由于LP2086是一种表面蛋白,荚膜多糖的表达可能会限制抗LP2086抗体与细菌表面表达的LP2086的结合。为了确定B群荚膜(Cap B)表达水平的变异性是否会干扰抗LP2086抗体与LP2086的结合,我们通过流式细胞术评估了抗Cap B抗体和抗LP2086抗体与1263株侵袭性临床MnB菌株表面结合的能力。所使用的一种抗LP2086单克隆抗体几乎能识别所有LP2086序列变体。我们的结果表明,Cap B的表达量与抗LP2086抗体的结合之间没有相关性。此外,MnB细菌对抗LP2086免疫血清裂解的敏感性与Cap B的表达水平无关。本文提供的数据表明,Cap B不会干扰抗体与MnB临床分离株外膜上表达的LP2086的结合。

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