Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.
China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing, China.
Hum Vaccin Immunother. 2019;15(12):2993-3002. doi: 10.1080/21645515.2019.1619404. Epub 2019 Jul 9.
Antibodies are effective alternative tools to combat infections caused by (PA), especially multi-drug-resistant PA. Thus, to solve the urgent need for an anti-PA antibody drug, we hypothesized that anti-PA intravenous immunoglobulins could be a practical attempt. Exotoxin A (ETA) is one of the most important factors for PA infection and is also a critical target for the development of immune interventions. In this study, a total of 320 sera were collected from healthy volunteers. The concentration of ETA-specific antibodies was determined by a Luminex-based assay and then purified by affinity chromatography. The purified IgGs were able to neutralize the cytotoxicity of ETA . We showed they had a prophylactic and therapeutic protective effect in PA pneumonia and ETA toxemia models. In addition, administration of nonspecific IgGs also provided partial protection. Collectively, our results provide additional evidence for IVIG-based treatment of infections caused by multi-drug-resistant PA and suggest that patients at high risk of PA pneumonia could be prophylactically treated with anti-ETA IgGs or even with nonspecific IgGs.
抗体是对抗(PA)引起的感染的有效替代工具,尤其是多药耐药性 PA。因此,为了解决对抗 PA 抗体药物的迫切需求,我们假设抗 PA 静脉注射免疫球蛋白可能是一种实用的尝试。肠毒素 A(ETA)是 PA 感染的最重要因素之一,也是免疫干预发展的关键靶点。在这项研究中,共从健康志愿者中收集了 320 份血清。ETA 特异性抗体的浓度通过基于 Luminex 的测定法确定,然后通过亲和层析进行纯化。纯化的 IgG 能够中和 ETA 的细胞毒性。我们表明它们在 PA 肺炎和 ETA 毒血症模型中具有预防和治疗保护作用。此外,给予非特异性 IgG 也提供了部分保护。总之,我们的结果为基于 IVIG 的多药耐药性 PA 引起的感染治疗提供了额外的证据,并表明高风险 PA 肺炎患者可以预防性地用抗 ETA IgG 治疗,甚至可以用非特异性 IgG 治疗。