ANTIGENIC AND MOLECULAR CHARACTERIZATION OF THE FUSION GLYCOPROTEIN OF RSV

呼吸道合胞病毒是引起下呼吸道感染的最常见原因 世界各地幼儿中的呼吸道疾病。《F》 该病毒的糖蛋白是病毒的重要靶点之一。 保护性免疫反应；然而，免疫是不完整和重复的 感染就会发生。此前，中和过程的详细地图 表位是基于一组鼠抗F抗体的能力而开发的 单抗中和14株耐药单抗 A2毒株的突变病毒。F单抗的反应性 与F-Marms组的抗体也按顺序进行了评估 以证实先前绘制的作战地图，并 证明了中和抵抗力与 没有抗体结合。在大多数情况下，marms不会绑定 选择抗体并验证了逃避中和的想法 是由于F内接触残基的特定突变所致 表位。此外，25株中和和非中和F单抗 被生物素化，并用于竞争性结合研究，以识别 F糖蛋白上至少有6个抗原点。这些生物素化的单抗 也被用来开发抗原性位点阻断分析，以便 分析RSV-F上特定区域的免疫应答 感染或免疫。初步研究表明，后- 感染具有相似中和能力的人和棉鼠血清 效价，在他们的抗F抗体反应的重复中变化。在.期间 来年将进行更多的研究以评估个人 自然感染后对F糖蛋白的免疫应答 免疫接种。作为这项工作的延伸，F单抗的反应性 将对合成多肽进行评估，以开发出表位 特异性定点酶联免疫吸附试验。

Respiratory syncytial virus is the most common cause of lower respiratory tract disease in young children worldwide. The F glycoprotein of this virus is one of the important targets of a protective immune response; however, immunity is incomplete and repeated infections occur. Previously, a detailed map of the neutralization epitopes was developed based on the ability of a panel of murine anti-F monoclonal antibodies to neutralize 14 monoclonal antibody resistant mutant viruses of the A2 strain. The reactivity of the F monoclonal antibodies with the panel of F MARMs in ELISA was also assessed in order to corroborate the operational map previously developed and to demonstrate a direct correlation between resistance to neutralization and absence of antibody binding. In most cases MARMs did not bind the selecting antibody and verified the idea that escape from neutralization was due to specific mutations in the contact residues within the F epitope. In addition, 25 neutralizing and non-neutralizing F MAbs have been biotinylated and used in competitive binding studies to identify at least 6 antigenic sites on the F glycoprotein. These biotinylated MAbs were also used to develop an antigenic site blocking assay in order to analyze the immune response to specific regions on RSV-F following infection or immunization. Preliminary studies have shown that post- infection human and cotton rat sera that have similar neutralization titers, vary in the repetoire of their anti-F antibody response. During the coming year additional studies will be done to evaluate individual immune responses to the F glycoprotein following natural infection or immunization. As an extension of this work, the reactivity of F MAbs with synthetic peptides will be evaluated in order to develop an epitope specific site-directed ELISA assay.