重组人源抗狂犬病毒单克隆抗体SO57、SOJB对狂犬病毒G蛋白亲和力的比较研究

一直以来，狂犬病是一种严重的人类致死性传染病。对狂犬病暴露后的预防主要是采用抗狂犬病毒免疫球蛋白（RIG）结合狂犬疫苗注射的方法。目前使用的两类RIG为人RIG（HRIG）和马RIG（ERIG），它们都是从免疫血清中分离出来的。由于HRIG成本高且产量少，质量难以控制，有潜在病毒污染的风险；而ERIG存在引起过敏反应等问题，因此，人们期望抗狂犬病毒人单克隆抗体能够取代RIG，用于狂犬病的暴露后预防。在狂犬病毒的多种免疫原物质中，狂犬病毒糖蛋白（以下简称G蛋白）是诱导产生抗病毒免疫保护的一种主要抗原，同时也是诱导产生病毒中和抗体并与之反应的唯一抗原。针对G蛋白的抗狂犬病毒抗体中和细胞外的狂犬病毒，并介导感染细胞的裂解及抗体依赖性的细胞毒性。在Dietzschold等发现的几株针对G蛋白的人单克隆中和抗体中，中和毒株的范围最广、抗体效价最高的为SO57，除此之外，SOJB也是目前研究较多的针对G蛋白的人单克隆中和抗体。

Affinity Comparison of Two Recombinant Human Anti-rabies Monoclonal Antibodies (SO57, SOJB) with Rabies Virus G Protein

It is desirable to develop potent rabies virus neutralizing human monoclonal antibodies(McAbs) to replace human or equine polyclonal immunoglobulin in the rabies virus postexposure treatment.Using BIAcore2000,affinity constants of McAbs with rabies virus glycoprotein(G protein) were determined taking human immunoglobulin as control,and affinity constants were calculated using BIAevaluation software.The affinity of McAb SOJB with rabies virus G protein was higher than that of SO57.Competition binding analyses ran on BIAcore2000 revealed that SO57 and SOJB competed for binding to rabies virus G protein,suggesting that epitopes recognized by SO57 and SOJB overlapped.Furthermore,the neutralizing potency of SO57 was significantly greater than that of SOJB as RFFIT showed.So it is desirable to develop SO57 firstly for rabies virus postexposure treatment.