Wyde P R, Moore D K, Hepburn T, Silverman C L, Porter T G, Gross M, Taylor G, Demuth S G, Dillon S B
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Pediatr Res. 1995 Oct;38(4):543-50. doi: 10.1203/00006450-199510000-00012.
Reshaped human MAb RSHZ19, which is specific for the surface fusion protein of respiratory syncytial virus (RSV) is in clinical development for the prevention and treatment of RSV-induced disease in human infants. The current studies profile lung virus clearance and evaluate lung histopathology in MAb-treated, RSV-infected cotton rats, a well characterized model of RSV infection. The highest dose of this MAb (10 mg/kg) administered parenterally 24 h before infection decreased subgroup A or B RSV lung titers to below detectable levels (> or = 2.3 log10 reduction), and significantly reduced lung virus titers (> or = 2.0 log10 reduction) when administered 96 h postinfection. Prophylactic administration of 10 mg/kg RSHZ19 was significantly more protective than 1000 mg/kg conventional human immune serum globulin (HSIg), and protective serum-neutralizing titers in MAb-treated animals (1:32, which correlated with approximately 40 micrograms/ml determined by anti-idiotype ELISA) were significantly lower than those reported previously for HSIg or for convalescent human serum (1:200-1:400). MAb concentration in lung lavages was determined by ELISA to be approximately 1% of the serum MAb concentration, but was not detectable by neutralization assay. The degree of lung histopathology in MAb-treated cotton rats was proportional to lung virus titer, and inversely proportional to the RSHZ19 dose administered. There was no evidence of exacerbated disease in the lungs of MAb-treated animals. These studies thus support the potential clinical utility of RSHZ19 MAb in the prevention and treatment of RSV-induced disease in humans.
重塑型人单克隆抗体RSHZ19特异性针对呼吸道合胞病毒（RSV）的表面融合蛋白，目前正处于临床开发阶段，用于预防和治疗人类婴儿由RSV引起的疾病。当前的研究描述了在接受单克隆抗体治疗的RSV感染棉鼠（一种特征明确的RSV感染模型）中肺部病毒清除情况，并评估了肺部组织病理学。在感染前24小时经肠胃外给予该单克隆抗体的最高剂量（10mg/kg）可使A或B亚组RSV肺部滴度降至可检测水平以下（降低≥2.3 log10），而在感染后96小时给予时可显著降低肺部病毒滴度（降低≥2.0 log10）。预防性给予10mg/kg的RSHZ19比1000mg/kg的传统人免疫血清球蛋白（HSIg）具有显著更强的保护作用，并且单克隆抗体治疗动物中的保护性血清中和滴度（1:32，通过抗独特型ELISA测定与约40μg/ml相关）显著低于先前报道的HSIg或恢复期人血清的滴度（1:200 - 1:400）。通过ELISA测定肺灌洗中的单克隆抗体浓度约为血清单克隆抗体浓度的1%，但通过中和试验无法检测到。接受单克隆抗体治疗的棉鼠的肺部组织病理学程度与肺部病毒滴度成正比，与给予的RSHZ19剂量成反比。在接受单克隆抗体治疗的动物肺部没有疾病加重的迹象。因此，这些研究支持了RSHZ19单克隆抗体在预防和治疗人类RSV诱导疾病方面的潜在临床应用价值。
