Kakuk T J, Soike K, Brideau R J, Zaya R M, Cole S L, Zhang J Y, Roberts E D, Wells P A, Wathen M W
Drug Safety Research and Infectious Diseases Research, Upjohn Co., Kalamazoo, Michigan.
J Infect Dis. 1993 Mar;167(3):553-61. doi: 10.1093/infdis/167.3.553.
Human respiratory syncytial virus (RSV) is the leading cause of severe bronchiolitis and pneumonia in infants. RSV vaccine development has been stifled for the past 23 years because infants vaccinated with formalin-inactivated (FI) RSV have experienced exacerbated disease upon RSV infection. This exacerbated disease phenomenon is poorly understood, in part because of the lack of a primate model that exhibits a similar exacerbated disease state. Vaccination of African green monkeys with either FI RSV or a genetically engineered subunit vaccine termed FG glycoprotein reduced replication of challenge virus. However, only vaccination with FI RSV induced an enhanced pulmonary pathologic response to RSV infection. Pulmonary inflammatory scores in the FG glycoprotein-vaccinated monkeys were no greater than in monkeys vaccinated with adjuvant alone. This is the first demonstration of RSV vaccine-induced enhanced pathology in a primate and illustrates that a subunit vaccine has the potential of circumventing this exacerbated disease phenomenon.
人类呼吸道合胞病毒（RSV）是婴儿严重细支气管炎和肺炎的主要病因。在过去23年里，RSV疫苗的研发一直受阻，因为接种了福尔马林灭活（FI）RSV的婴儿在感染RSV后病情会加重。这种病情加重的现象目前还了解甚少，部分原因是缺乏能呈现类似病情加重状态的灵长类动物模型。用FI RSV或一种名为FG糖蛋白的基因工程亚单位疫苗对非洲绿猴进行接种，均可减少攻击病毒的复制。然而，只有接种FI RSV会引发对RSV感染增强的肺部病理反应。接种FG糖蛋白的猴子的肺部炎症评分并不高于仅接种佐剂的猴子。这是首次在灵长类动物中证明RSV疫苗诱导的病理反应增强，并表明亚单位疫苗有潜力规避这种病情加重的现象。
