A Recombinant Clumping Factor A-Containing Vaccine Induces Functional Antibodies to Staphylococcus aureus That Are Not Observed after Natural Exposure
A Recombinant Clumping Factor A-Containing Vaccine Induces Functional Antibodies to Staphylococcus aureus That Are Not Observed after Natural Exposure
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DOI：
10.1128/cvi.00354-12
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发表时间：
2012-10-01
影响因子：
--
通讯作者：
Donald, Robert G. K.
中科院分区：
文献类型：
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作者：
Hawkins, Julio;Kodali, Srinivas;Donald, Robert G. K.
金黄色葡萄球菌是一种引起毁灭性疾病的革兰氏阳性病原体，其发病机制依赖于与宿主细胞因子的相互作用。葡萄球菌凝集因子A （ClfA）是一种高度保守的纤维蛋白原（Fg）结合蛋白和毒力因子，有助于宿主组织粘附和感染的启动。目前正在研究ClfA作为葡萄球菌疫苗的可能成分。我们报告了一种针对clfa介导的结合特异性的fg结合测定的发展。通过该实验，我们发现，尽管存在抗clfa抗体，未接种疫苗的受试者的人血清无法阻止金黄色葡萄球菌与fg涂层表面的结合。相反，含有clfa的重组疫苗引发的抗体能够阻断多种临床相关葡萄球菌菌株与Fg的clfa依赖性结合。这些功能性抗体也能够取代已经与Fg结合的金黄色葡萄球菌，这表明ClfA的配体结合活性可以通过接种有效地中和。
Staphylococcus aureus is a Gram-positive pathogen that causes devastating disease and whose pathogenesis is dependent on interactions with host cell factors. Staphylococcal clumping factor A (ClfA) is a highly conserved fibrinogen (Fg)-binding protein and virulence factor that contributes to host tissue adhesion and initiation of infection. ClfA is being investigated as a possible component of a staphylococcal vaccine. We report the development of an Fg-binding assay that is specific for ClfA-mediated binding. Using the assay, we show that despite the presence of anti-ClfA antibodies, human sera from unvaccinated subjects are unable to prevent the binding of S. aureus to an Fg-coated surface. In contrast, antibodies elicited by a recombinant ClfA-containing vaccine were capable of blocking the ClfA-dependent binding of a diverse and clinically relevant collection of staphylococcal strains to Fg. These functional antibodies were also able to displace S. aureus already bound to Fg, suggesting that the ligand-binding activity of ClfA can be effectively neutralized through vaccination.