Everitt D E, Davis C B, Thompson K, DiCicco R, Ilson B, Demuth S G, Herzyk D J, Jorkasky D K
Department of Medicine, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
J Infect Dis. 1996 Sep;174(3):463-9. doi: 10.1093/infdis/174.3.463.
Single ascending doses of RSHZ19 (also known as SB 209763), a humanized monoclonal antibody (MAb) directed to the fusion protein of respiratory syncytial virus, were administered to healthy men to evaluate the safety, pharmacokinetics, antigenicity, and fusion inhibition (FI) activity of RSHZ19. Doses of RSHZ19 (0.025-10.0 mg/kg) or placebo were infused over 30 min, and subjects were followed for 10 weeks. Plasma concentrations of RSHZ19 and RSHZ19-specific antibodies were determined by ELISAs. FI titers were used to evaluate the ability of plasma to inhibit virus-induced fusion of VERO cells previously infected with RS Long strain virus. Twenty-six subjects, mean age 24, completed the study. RSHZ19 was safe and well tolerated, and no subject developed antibodies to RSHZ19 during follow-up. RSHZ19 had low plasma clearance and a half-life of approximately 23 days, similar to native IgG. Increases in FI titers relative to pretreatment levels were seen 24 h after MAb administration in all 4 subjects given 10 mg/kg and in 2 of 4 given 5 mg/kg.
将人源化单克隆抗体（MAb）RSHZ19（也称为SB 209763），其针对呼吸道合胞病毒的融合蛋白，以单次递增剂量给予健康男性，以评估RSHZ19的安全性、药代动力学、抗原性和融合抑制（FI）活性。将RSHZ19（0.025 - 10.0mg/kg）剂量或安慰剂在30分钟内输注，对受试者随访10周。通过酶联免疫吸附测定法（ELISA）测定RSHZ19和RSHZ19特异性抗体的血浆浓度。FI效价用于评估血浆抑制先前感染RS Long株病毒的VERO细胞的病毒诱导融合的能力。26名受试者，平均年龄24岁，完成了该研究。RSHZ19安全且耐受性良好，在随访期间没有受试者产生针对RSHZ19的抗体。RSHZ19具有低血浆清除率，半衰期约为23天，与天然IgG相似。在给予10mg/kg的所有4名受试者以及给予5mg/kg的4名受试者中的2名中，在给予单克隆抗体24小时后观察到FI效价相对于预处理水平增加。
