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，在美国每年造成120万人住院。20世纪60年代早期的一次失败的疫苗试验阻碍了RSV疫苗的发展，在那次试验中，接种了疫苗的儿童没有受到保护，无法抵御随后的自然感染，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进行的实验表明，严重RSV疾病的发生与病毒特异性Th2 CD4 T细胞和嗜酸性粒细胞的募集和脱颗粒的诱导有关。RSV的G糖蛋白和含有明矾等佐剂的灭活病毒疫苗可诱导与疫苗增强型疾病综合征相关的这些类型的免疫反应。

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 G glycoprotein of RSV and killed virus vaccines containing adjuvants such as alum induce these types of immune responses associated with the vaccine-enhanced disease syndrome. Dendritic cells are important for processing antigen and initiating immune responses. Understanding their interaction with RSV may reveal the reasons for relatively short-lived immunity induced by natural RSV infection. CD4 T cells can influence and regulate the function of other immune effectors including CD8 T cells. In addition to the potential role of Th2 CD4 T cells in RSV pathogenesis as mentioned above, T regulatory cells have properties that suggest they may be important in RSV immunity and pathogenesis.