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

RSV 发病机制中导致免疫增强性疾病的因素

• 批准号: 8336383
• 负责人: Barney Graham
• 金额: $ 62.36万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336383
• 关键词: Adjuvant; Adult; Animal Model; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Maturation; Cell physiology; Child; Childhood Asthma; Cytotoxic T-Lymphocytes; Dendritic Cells; Development; Disease; Exposure to; Glycoproteins; Goals; Hospitalization; Immune; Immune response; Immunity; Immunization; Immunologics; Infection; Integration Host Factors; Interleukin-4; Life; Mediating; Neonatal; Pathogenesis; Property; Recording of previous events; Regulatory T-Lymphocyte; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Tract Infections; Respiratory syncytial virus; Respiratory syncytial virus RSV G glycoprotein; Role; Syndrome; T cell response; T-Lymphocyte; Vaccinated; Vaccine Therapy; Vaccines; Viral; Virus; Virus Activation; Virus Diseases; aluminum sulfate; antigen processing; eosinophil; experience; human subject; killings; mouse model; research study; response; vaccine development; virus pathogenesis

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.

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> 120，000例住院治疗。RSV疫苗的开发因20世纪60年代初疫苗试验失败的历史而受到阻碍，在该试验中，接种疫苗的儿童并没有受到随后自然感染的保护，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 CD4 T细胞的诱导以及嗜酸性粒细胞募集和脱粒相关。RSV的G糖蛋白和含有佐剂如明矾的灭活病毒疫苗诱导与疫苗增强疾病综合征相关的这些类型的免疫应答。 树突状细胞对于处理抗原和启动免疫应答是重要的。了解它们与RSV的相互作用可能揭示天然RSV感染诱导的相对短暂的免疫力的原因。CD4 T细胞可以影响和调节包括CD8 T细胞在内的其他免疫效应子的功能。除了如上所述的Th2 CD4 T细胞在RSV发病机制中的潜在作用之外，T调节细胞具有表明它们在RSV免疫和发病机制中可能是重要的性质。