Rivera Johanna, Nakouzi Antonio, Abboud Nareen, Revskaya Ekaterina, Goldman David, Collier R John, Dadachova Ekaterina, Casadevall Arturo
Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Infect Immun. 2006 Jul;74(7):4149-56. doi: 10.1128/IAI.00150-06.
Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. anthracis lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs to PA, MAbs 7.5G and 10F4. These MAbs did not compete for binding to PA, consistent with specificities for different epitopes. The MAbs were tested for their ability to protect a monolayer of cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G, the most-neutralizing MAb, bound to domain 1 of PA and reduced LeTx toxicity in BALB/c mice. Remarkably, MAb 7.5G provided protection without blocking the binding of PA or lethal factor or the formation of the PA heptamer complex. However, MAb 7.5G slowed the proteolytic digestion of PA by furin in vitro, suggesting a potential mechanism for Ab-mediated protection. These observations indicate that some Abs to domain 1 can contribute to host protection.
对炭疽杆菌毒素的抗体（Ab）反应具有保护作用，但已报道的保护性单克隆抗体（MAb）相对较少。保护性抗原（PA）对于炭疽杆菌致死毒素（LeTx）和水肿毒素的作用至关重要。在本研究中，我们制备了两种针对PA的单克隆抗体，即单克隆抗体7.5G和10F4。这些单克隆抗体在与PA的结合上不相互竞争，这与它们针对不同表位的特异性一致。测试了这些单克隆抗体保护单层培养巨噬细胞免受毒素介导的细胞毒性的能力。最具中和作用的单克隆抗体7.5G与PA的结构域1结合，并降低了BALB/c小鼠体内LeTx的毒性。值得注意的是，单克隆抗体7.5G提供了保护作用，但并未阻断PA或致死因子的结合或PA七聚体复合物的形成。然而，单克隆抗体7.5G在体外减缓了弗林蛋白酶对PA的蛋白水解消化，提示了抗体介导保护作用的潜在机制。这些观察结果表明，一些针对结构域1的抗体可有助于宿主保护。
