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，每年在美国导致> 120,000次住院。 1960年代初期的一项疫苗试验失败的疫苗试验病史阻碍了RSV疫苗的开发，其中未能保护接种疫苗的儿童免受随后的自然感染的保护，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进行的实验表明，严重的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糖蛋白并杀死了含有明矾等佐剂的病毒疫苗，诱导了与疫苗增强疾病综合征相关的这些类型的免疫反应。 树突状细胞对于加工抗原和引发免疫反应很重要。了解它们与RSV的相互作用可能会揭示自然RSV感染引起的相对短暂免疫力的原因。 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。除了上述TH2 CD4 T细胞在RSV发病机理中的潜在作用外，T调节细胞具有表明它们在RSV免疫和发病机理中可能很重要。