Shannon O, Uekotter A, Flock J-I
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Scand J Immunol. 2006 Mar;63(3):184-90. doi: 10.1111/j.1365-3083.2006.01735.x.
Staphylococcus aureus is a significant cause of acute and chronic infection and boasts a diverse array of virulence factors. S. aureus produces and secretes a protein, extracellular fibrinogen (Fg)-binding protein (Efb), which contributes to virulence in wound infection. Efb binds to both Fg and platelets and inhibits platelet function in vitro and in vivo. In this study, we have characterized the antibody response against Efb. Antibodies generated in response to immunization with Efb can neutralize the biological effects of Efb. Hyperimmune sheep immunoglobulin (Ig)G against Efb blocked the binding of Efb to Fg and prevented Efb-mediated inhibition of platelet aggregation. Furthermore, these antibodies cross-reacted with coagulase and blocked coagulase activity in plasma. Immunization of mice with Efb resulted in the generation of high titre specific antibodies. When subjected to a foreign-body-associated wound infection, the vaccinated animals developed significantly less severe wound infection than the unvaccinated controls. Also, human IgG against Efb was prepared from commercial IgG pools; however, the monospecific human anti-Efb that was enriched was unable to neutralize Efb. We conclude that immunization with Efb is required in order to generate a protective antibody response to Efb from S. aureus.
金黄色葡萄球菌是急性和慢性感染的重要病因，拥有多种毒力因子。金黄色葡萄球菌产生并分泌一种蛋白质，即细胞外纤维蛋白原（Fg）结合蛋白（Efb），它在伤口感染中对毒力起作用。Efb能与Fg和血小板结合，并在体外和体内抑制血小板功能。在本研究中，我们已对针对Efb的抗体反应进行了表征。针对用Efb免疫产生的抗体可中和Efb的生物学效应。针对Efb的超免疫羊免疫球蛋白（Ig）G可阻断Efb与Fg的结合，并防止Efb介导的血小板聚集抑制。此外，这些抗体与凝固酶发生交叉反应，并阻断血浆中的凝固酶活性。用Efb免疫小鼠可产生高滴度的特异性抗体。当遭受与异物相关的伤口感染时，接种疫苗的动物伤口感染的严重程度明显低于未接种疫苗的对照。而且，从商业IgG库中制备了针对Efb的人IgG；然而，富集的单特异性人抗Efb无法中和Efb。我们得出结论，需要用Efb进行免疫，以便产生针对金黄色葡萄球菌Efb的保护性抗体反应。
