Factors Contributing To Immune-Enhanced Disease In The Pathogenesis of RSV

呼吸道合胞病毒(RSV)感染是幼儿呼吸道感染的主要原因，在美国每年导致12万人住院治疗。20世纪60年代初的一次疫苗试验失败的历史阻碍了RSV疫苗的开发，在那次试验中，接种疫苗的儿童没有受到保护，不会受到随后的自然感染，而是经历了更严重的疾病。随后在动物模型和人类受试者中的实验表明，严重RSV疾病的发生与病毒特异性Th2、CD4T细胞的诱导以及嗜酸性粒细胞的招募和脱颗粒有关。RSV的假定附着G糖蛋白和含有明胶等佐剂的灭活病毒疫苗在诱导这种增强疾病的免疫反应方面特别有效。这些研究的目的是1)确定RSV免疫的确切成分，在随后暴露于病毒时易患严重的RSV疾病；2)确定RSV的结构如何导致疾病；3)对RSV的发病机制有更好的了解，合理地设计RSV疫苗，在不增加疾病的情况下预防感染。

Respiratory syncytial virus (RSV) infection is the primary cause of respiratory infection in young children, causing >120,000 hospitalizations in the US annually. RSV vaccine development has been hampered by the history of a failed vaccine trial in the early 1960s in which vaccinated children were not protected against subsequent natural infection but rather experienced more severe disease. Subsequent experiments in animal models and human subjects suggest the occurrence of severe RSV disease correlates with the induction of virus-specific Th2 CD4+ T cells and eosinophil recruitment and degranulation. The putative attachment G glycoprotein of RSV and killed virus vaccines containing adjuvants such as alum are particularly effective in inducing such disease-enhancing immune responses. The purposes of these studies are 1) to define the precise components of RSV immunity that predispose for severe RSV disease upon subsequent exposure to the virus, 2) to determine how the structure of RSV contributes to disease, and 3) with this better understanding of RSV pathogenesis, to rationally design RSV vaccines that protect against infection without enhancing disease.