狂犬病暴露后预防性单克隆抗体药物研究进展  

Research progress on prophylactic monoclonal antibody drugs for rabies post exposure prophylaxis

作　　者：吴梦[1,2,5] 张浩 刘雪芹 涂长春[7] 刘艳 葛良鹏 WU Meng;ZHANG Hao;LIU Xueqin;TU Changchun;LIU Yan;GE Liangpeng(Chongqing Academy of Animal Sciences,Chongqing 402460,China;National Center of Technology Innovation for Pigs,Chongqing 402460,China;Key Laboratory of Pig Industry Sciences,Ministry of Agriculture,Chongqing 402460,China;Chongqing Key Laboratory of Pig Industry Sciences,Chongqing 402460,China;Chongqing animal resources center for translational medical application and engineering,Chongqing 402460,China;Chongqing CAMAB BIOTECH Ltd.,Chongqing 402460,China;Changchun Veterinary Research Institute,ChineseAcademy of Agricultural Sciences,Changchun 130000,China)

机构地区：[1]重庆市畜牧科学院,重庆402460 [2]国家生猪技术创新中心,重庆402460 [3]农业部养猪科学重点实验室,重庆402460 [4]养猪科学重庆市市级重点实验室,重庆402460 [5]重庆市医用动物资源开发与转化应用工程技术中心,重庆402460 [6]重庆金迈博生物科技有限公司,重庆402460 [7]中国农业科学院长春兽医研究所,长春130000

出　　处：《生物学杂志》2024年第5期100-106,共7页Journal of Biology

基　　金：重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0042);重庆市科研机构绩效激励引导专项项目(cstc2022jxjl80012);重庆市科研机构绩效激励引导专项项目(22536)。

摘　　要：简要介绍狂犬病的流行现状、发病机制、狂犬病病毒G蛋白中和抗原位点及其单克隆抗体的中和机制。重点介绍目前全球已上市或处于研发阶段的多种狂犬病病毒单克隆抗体药物的筛选发现技术、识别位点、作用方式以及体内外病毒中和效果,分析上述单克隆抗体在目前狂犬病暴露后治疗的应用推广中存在的问题,并针对当前狂犬病免疫球蛋白存在的血源供应、中和效价、质量控制及潜在病毒感染等问题,指出狂犬病病毒单克隆抗体研发的重要性,尤其是抗体的中和效价和中和广度,进而提出针对狂犬病病毒遗传谱系Ⅱ/Ⅲ的全人源单克隆抗体开发,以及针对G蛋白多个抗原位点的单克隆抗体鸡尾酒(mAb cocktail)疗法是当前在狂犬病暴露后预防性单克隆抗体药物研发中亟待解决的问题。The current epidemic status,pathogenesis of rabies,the neutralizing antigen sites of RABV glycoprotein and the neutralization mechanism of the monoclonal antibodies against RABV infection were briefly described.The screening techniques,recognition sites,action mechanism and neutralization effects of almost all of the monoclonal antibodies against RABV which are currently available on the market or under development worldwide were also introduced.The paper further analyzed the problems existing in the application of the above mentioned monoclonal antibodies and the disadvantage of rabies immune globulin in the current post-exposure prophylaxis of RABV infection,including the limited blood supply,neutralization titers,the quality control and potential virus infection,which implies that the more attention should be paid to the development of full human monoclonal antibodies against RABV,especially for their neutralization efficiency and breadth.Taken together,the full human monoclonal antibodies drugs targeting the phylogroupⅡ/Ⅲof glycoprotein and the cocktail targeting multiple antigenic sites are potential efficient strategy to the development of post-exposure prophylaxis of RABV infection.

关 键 词：狂犬病 狂犬病病毒 单克隆抗体 中和抗体 抗原表位 

分 类 号：R392.11[医药卫生—免疫学] Q785[医药卫生—基础医学]