Intercell AG, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
Vaccine. 2011 May 31;29(24):4116-24. doi: 10.1016/j.vaccine.2011.03.100. Epub 2011 Apr 13.
Group B streptococcus remains an important neonatal pathogen in spite of widely adopted intrapartum antibiotic administration; therefore immune prophylaxis for GBS infections is highly warranted. In passive immunization and lethal challenge studies with multiple GBS strains, we characterized the protective effect of rabbit polyclonal and murine monoclonal antibodies specific for four multi-functional cell wall anchored proteins, FbsA, BibA, PilA and PilB. Single specificity rabbit sera or mAbs induced high level, but strain dependent protection, while their combinations resulted in superior and broad efficacy against all GBS strains tested. Polyclonal and monoclonal antibodies specific for the pilus proteins exerted very potent opsonophagocytic killing activity in vitro and required the Fc domain for protection in vivo. In contrast, FbsA and BibA specific antibodies failed to show OPK activity, but their Fab fragments fully protected animals, suggesting that blocking the function of these proteins was the major mode of action. These data are supportive for developing immune prophylaxis with human mAbs for prematurely born neonates who receive low levels of antibodies by maternofetal transport and are characterized by not fully developed phagocytic and complement activity.
B 群链球菌仍然是一种重要的新生儿病原体，尽管已经广泛采用了分娩时抗生素给药；因此，针对 GBS 感染的免疫预防具有高度的必要性。在使用多种 GBS 菌株进行被动免疫和致死性挑战研究中，我们描述了针对四个多功能细胞壁锚定蛋白 FbsA、BibA、PilA 和 PilB 的兔多克隆和鼠单克隆抗体的保护作用。单一特异性兔血清或 mAb 诱导高水平但菌株依赖性的保护，而它们的组合则导致对所有测试的 GBS 菌株具有优越和广泛的疗效。针对菌毛蛋白的多克隆和单克隆抗体在体外表现出非常有效的调理吞噬杀伤活性，并且在体内需要 Fc 结构域来保护。相比之下，FbsA 和 BibA 特异性抗体未能显示 OPK 活性，但它们的 Fab 片段完全保护了动物，表明阻断这些蛋白的功能是主要的作用模式。这些数据支持开发针对通过母婴转运接受低水平抗体且吞噬和补体活性尚未完全发育的早产儿的人类 mAb 免疫预防，
