Beudeker Coco R, van Dalen Rob, Ruyken Maartje, de Haas Carla J C, Scheepmaker Lisette M, Vijlbrief Daniel, Lely A Titia, van Kessel Kok P M, van der Bruggen Jan-Tom, Rooijakkers Suzan H M, Salazar Leire Aguinagalde, van der Flier Michiel
Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Department of Paediatric Infectious Diseases and Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Sci Rep. 2025 Aug 25;15(1):31243. doi: 10.1038/s41598-025-15490-y.
Staphylococcus epidermidis is a major cause of late onset sepsis in extremely preterm neonates. Antibody therapies are considered as an interesting strategy to prevent sepsis. However, previous clinical trials with intravenous immunoglobulin (IVIG) and a monoclonal antibody (mAb) targeting staphylococcal lipoteichoic acid (LTA) (Pagibaximab) failed to show significant protection from invasive infections in extremely preterm neonates. Here we use an age-specific in vitro platform to compare immune protection by Pagibaximab with two other mAbs recognizing invasive S. epidermidis in the context of the neonatal immune system. We demonstrate poor activity of Pagibaximab in inducing complement C3b opsonization and neutrophil opsonophagocytosis in neonatal plasma. MAbs CR5133 and CR6453 [recognizing wall teichoic acid (WTA)] potently induced S. epidermidis opsonophagocytosis in an (extreme) preterm reconstituted whole blood model, especially after introduction of hexamer-enhancing mutations in the IgG-Fc tail. In conclusion, using age-specific in vitro assays, we show that mAbs with strong complement-inducing potential may be effective in preventing neonatal bacterial sepsis in extreme preterm neonates.
表皮葡萄球菌是极早产儿晚发型败血症的主要病因。抗体疗法被认为是预防败血症的一种有前景的策略。然而，先前针对静脉注射免疫球蛋白（IVIG）和一种靶向葡萄球菌脂磷壁酸（LTA）的单克隆抗体（mAb）（帕吉昔单抗）的临床试验未能显示出对极早产儿侵袭性感染有显著保护作用。在此，我们使用特定年龄的体外平台，在新生儿免疫系统背景下，比较帕吉昔单抗与另外两种识别侵袭性表皮葡萄球菌的单克隆抗体的免疫保护作用。我们证明帕吉昔单抗在诱导新生儿血浆中补体C3b调理作用和中性粒细胞调理吞噬作用方面活性较差。单克隆抗体CR5133和CR6453 [识别壁磷壁酸（WTA）] 在（极）早产重组全血模型中能有效诱导表皮葡萄球菌的调理吞噬作用，特别是在IgG-Fc尾部引入六聚体增强突变后。总之，通过特定年龄的体外试验，我们表明具有强大补体诱导潜力的单克隆抗体可能对预防极早产儿的新生儿细菌性败血症有效。
