NEUTRALIZATION OF RESPIRATORY VIRUSES BY SECRETORY IGA

分泌型 IGA 中和呼吸道病毒

• 批准号: 3082433
• 负责人: MARY B MAZANEC
• 金额: $ 7.78万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3082433
• 关键词: antiviral antibody; dimer; immunoglobulin A; laboratory mouse; laboratory rabbit; monoclonal antibody; monomer; mucosa; parainfluenza virus type 1; passive immunization; protein transport; radiotracer; respiratory epithelium; respiratory virus; secretory immune system; tissue /cell culture

Based on the knowledge that the mucosal immune system and its predominant effector, secretory IgA, forms the first line of defense at the interface between the pulmonary epithelial surface an the external environment and that resistance to respiratory viral infections correlates with the presence of viral specific IgA antibodies in the mucosal secretions, this proposal seeks to determine the mechanism(s) by which secretory IgA neutralizes virus at the mucosal surface. This project will employ a model system of a natural respiratory pathogen of mice, Sendai virus, a member of the parainfluenza group. A series of anti-Sendai IgA monoclonal antibodies has been generated, and characterized for antigenic specificity and in vitro biologic activities. These anti- viral IgA monoclonal antibodies will be used in three major kinds of studies. First, passive immunization studies have been designed to determine and compare the protection afforded by locally versus systemically administered antibody of IgA and other isotypes against subsequent viral challenge. Second, radiolabeled monoclonal antibodies will be used to examine the transport kinetics of serum dimeric and monomeric IgA as compared to IgG into the pulmonary mucosal secretions. Third, the ability of IgA antibody to neutralize virus within mucosal epithelial cells in a polarized tissue culture system will be assessed. Information generated from these experiments should aide in the development of more effective strategies for immunization against common human respiratory viral pathogens.

基于粘膜免疫系统及其 主要效应子，分泌型 IgA，形成第一线 肺上皮表面之间界面的防御 外部环境和呼吸阻力 病毒感染与病毒特异性 IgA 的存在相关 粘膜分泌物中的抗体，该提案旨在 确定分泌型 IgA 中和的机制 病毒在粘膜表面。 该项目将采用一个模型 小鼠自然呼吸道病原体系统，仙台病毒， 副流感群的成员。 抗仙台IgA系列 单克隆抗体已生成，并进行了表征 抗原特异性和体外生物活性。 这些反 病毒IgA单克隆抗体将三大类应用 的研究。 首先，被动免疫研究已 旨在确定和比较所提供的保护 局部与全身施用 IgA 和其他抗体 针对随后的病毒攻击的同种型。 二、放射性标记 单克隆抗体将用于检查运输 血清二聚体和单体 IgA 与 IgG 相比的动力学 进入肺粘膜分泌物。 三、IgA能力 中和粘膜上皮细胞内病毒的抗体 将评估极化组织培养系统。 信息 这些实验产生的结果应该有助于开发 更有效的针对常见疾病的免疫策略 人类呼吸道病毒病原体。