Fisher R G, Johnson J E, Dillon S B, Parker R A, Graham B S
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
J Infect Dis. 1999 Sep;180(3):708-13. doi: 10.1086/314965.
Respiratory syncytial virus (RSV) is the most significant viral cause of lower respiratory tract disease in infants and children. This study tested the hypothesis that a humanized murine monoclonal antibody (MAb) would protect against RSV infection in mice and have minimal suppressive effect upon the immune response because it is directed against a single epitope. A humanized murine MAb (RSHZ19) was tested for both prophylaxis and treatment of RSV infection in BALB/c mice and compared with a polyclonal product. Mice were rechallenged when passively administered antibody was undetectable (day 104). RSHZ19 reduced virus titer and protected against illness when used in prophylaxis and effected rapid virus clearance when used as treatment. Polyclonal antibody was also an effective prophylaxis but required 200 times the dose in total protein. Peak neutralizing antibody responses were delayed and somewhat suppressed in the prophylactically treated groups, but mice were protected against infection on rechallenge. Secondary antibody response to rechallenge in passively immunized mice was equal to that in untreated mice.
呼吸道合胞病毒(RSV)是婴幼儿下呼吸道疾病最重要的病毒病因。本研究检验了这样一个假设:一种人源化鼠单克隆抗体(MAb)可保护小鼠免受RSV感染,并且由于其针对单一表位,对免疫反应的抑制作用最小。对一种人源化鼠单克隆抗体(RSHZ19)进行了在BALB/c小鼠中预防和治疗RSV感染的测试,并与一种多克隆产品进行了比较。当被动给予的抗体检测不到时(第104天),对小鼠进行再次攻击。RSHZ19在用于预防时可降低病毒滴度并预防疾病,在用作治疗时可实现快速病毒清除。多克隆抗体也是一种有效的预防措施,但所需总蛋白剂量是其200倍。在预防性治疗组中,峰值中和抗体反应延迟且有所抑制,但小鼠在再次攻击时受到保护而未被感染。被动免疫小鼠对再次攻击的二次抗体反应与未治疗小鼠相同。