NEUTRALIZATION OF RESPIRATORY VIRUSES BY SECRETORY IGA

基于粘膜免疫系统及其 主要的效应，分泌型伊加，形成第一线， 在肺上皮细胞表面和肺上皮细胞表面之间的界面处的防御 外部环境和呼吸阻力 病毒感染与病毒特异性伊加的存在相关 粘膜分泌物中的抗体，该建议旨在 确定分泌型伊加中和 粘膜表面的病毒。 本项目将采用一种模式 系统的一种自然的呼吸道病原体，仙台病毒， 副流感病毒组的成员。 一系列抗仙台伊加 已经产生了单克隆抗体，并表征了 抗原特异性和体外生物活性。 这些反- 病毒伊加单克隆抗体将用于三种主要类型 的研究。 首先，被动免疫研究已经被 旨在确定和比较 局部与全身施用的伊加和其他抗体 同种型抵抗随后的病毒攻击。 第二，放射性标记 单克隆抗体将被用来检查运输 与IgG相比，血清二聚体和单体伊加的动力学 进入肺粘膜分泌物 三、伊加的能力 抗体中和粘膜上皮细胞内的病毒， 将评估极化组织培养系统。 信息 从这些实验中产生的结果应该有助于开发 更有效的免疫战略， 人类呼吸道病毒病原体。

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.