切换至 "中华医学电子期刊资源库"
高级检索
中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 229 -233. doi: 10.3877/cma.j.issn.1674-1358.2022.04.002

综述

狂犬病免疫球蛋白研究与应用进展
张信1, 高标2, 陈启明1, 吴定宇1, 曹恒昌1, 范昭1,†()   
  1. 1. 518034　深圳市，北京大学深圳医院急诊科
    2. 200433　上海，海军军医大学教研保障中心
  • 收稿日期:2021-11-29 出版日期:2022-08-15
  • 通信作者: 范昭
  • 基金资助:
    军队重点学科建设项目(No. HL21JD1206); 上海海洋医学出版中心（培）(No. 2018-775-2-1)

Progress on research and application of rabies immunoglobulin

Xin Zhang1, Biao Gao2, Qiming Chen1, Dingyu Wu1, Hengchang Cao1, Zhao Fan1,†()   

  1. 1. Peking University Shenzhen Hospital, Emergency Department, Shenzhen 518034, China
    2. Support Center of Teaching and Research, Naval Medical University, Shanghai 200433, China
  • Received:2021-11-29 Published:2022-08-15
  • Corresponding author: Zhao Fan
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

张信, 高标, 陈启明, 吴定宇, 曹恒昌, 范昭. 狂犬病免疫球蛋白研究与应用进展[J]. 中华实验和临床感染病杂志(电子版), 2022, 16(04): 229-233.

Xin Zhang, Biao Gao, Qiming Chen, Dingyu Wu, Hengchang Cao, Zhao Fan. Progress on research and application of rabies immunoglobulin[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(04): 229-233.

狂犬病是一种危险的人畜共患疾病，仍可防不可治。暴露后免疫是预防狂犬病的唯一方法，严重的Ⅲ级暴露则需注射狂犬病免疫球蛋白。本文阐述狂犬病毒的结构和致病途径，回顾狂犬病免疫球蛋白应用现状以及抗狂犬病毒单克隆抗体的研发和生产，分析免疫球蛋白在狂犬病临床防治应用中存在的问题和策略进展，认为处于临床试验阶段的抗狂犬病毒单克隆抗体研发是未来临床应用的发展方向。

关键词: 狂犬病毒, 暴露后免疫, 狂犬病免疫球蛋白, 人源单克隆抗体

Rabies is a dangerous zoonotic disease which is preventable but still untreatable. Immunization after exposure is the only measure to prevent rabies. For the severe level Ⅲ exposure, injection of rabies immunoglobulin is the important measure. This article summarizes the structure and pathogenesis of rabies virus, and reviews the application of rabies immunoglobulin, as well as the research and development of anti-rabies virus monoclonal antibody. The problems and progress in strategies in the clinical application of immunoglobulin for the prevention and treatment of rabies are also discussed. It suggests that the research and development of anti-rabies monoclonal antibody in the clinical trial stage is the future of clinical application.

Key words: Rabies virus, Post-exposure immunization, Immunoglobulin, Human monoclonal antibody
图1 狂犬病毒形状与抗原位点注：A：病毒呈典型的子弹状[5]；B：病毒表面糖蛋白抗原位点示意图[12]
表1 狂犬病暴露后分类及预防
暴露类型 接触方式 暴露程度 暴露后预防处置
Ⅰ 符合以下情况之一者：
① 接触/喂养动物；
②皮肤完整被舔舐；
③ 皮肤完整接触狂犬病动物/人狂犬病病例的分泌物或排泄物		 无 确认接触方式可靠则不需处置
Ⅱ 符合以下情况之一者：
①裸露皮肤轻咬；
②无出血的轻微抓伤/擦伤		 轻度 ①伤口处理；
②接种狂犬病疫苗
Ⅲ 符合以下情况之一者：
① 单处/多处贯穿伤/抓伤；
②破损皮肤被舔舐；
③开放性伤口/黏膜被舔舐；
④ 暴露于蝙蝠		 严重 ① 伤口处理；
②注射狂犬病被动免疫制剂（抗狂犬病血清/狂犬病人免疫球蛋白）；
③注射狂犬病疫苗
[1]
Hampson K, Coudeville L, Lembo T, et al. Estimating the global burden of endemic canine rabies[J]. PLoS Negl Trop Dis,2015,9(4):e3709.
[2]
Moore SM. Rabies: current preventive strategies[J]. Vet Clin North Am Small Anim Pract,2019,49(4):629-641.
[3]
佚名. 美国CDC宣布已根除犬类狂犬病[J]. 中国动物保健, 2007,8(12):121.
[4]
Gogtay NJ, Nagpal A, Mallad A, et al. Demographics of animal bite victims & management practices in a tertiary care institute in Mumbai, Maharashtra, India[J]. Indian J M Ed Res,2014,139:459-462.
[5]
Fooks AR, Cliquet F, Finke S, et al. Rabies[J]. Nat Rev Dis Primers,2017,3(17091):1-19.
[6]
Mueller T, Dietzschold B, Ertl H, et al. Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans[J]. PLoS Neglect Trop D,2009,3(11):e542.
[7]
Bharti OK, Madhusudana SN, Gaunta PL, et al. Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies[J]. Hum Vacc Immunother, 2016,12(3):837-842.
[8]
World Health Organization. Rabies vaccines: WHO position paper, April 2018-recommendations[J]. Vaccine,2018,36(37):5500-5503.
[9]
Gogtay NJ, Munshi R, Narayana DHA, et al. Comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for postexposure prophylaxis: A phase 2/3, randomized, single-blind, noninferiority, controlled study[J]. Clin Infect Dis,2018,66(3):387-395.
[10]
Benmansour A, Leblois H, Coulon P, et al. Antigenicity of rabies virus glycoprotein[J]. J Virol,1991,65:4198-4203.
[11]
Marissen WE, Kramer RA, Rice A, et al. Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: fine mapping and escape mutant analysis[J]. J Virol,2005,79(8):4672-4678.
[12]
Ilina EN, Larina MV, Aliev TK, et al. Recombinant monoclonal antibodies for rabies post-exposure prophylaxis[J]. Biochemistry, 2018,83(1):1-12.
[13]
Lentz TL, Hawrot E, Wilson PT. Synthetic peptides corresponding to sequences of snake venom neurotoxins and rabies virus glycoprotein bind to the nicotinic acetylcholine receptor[J]. Proteins,1987,2(4):298-307.
[14]
Lewis P, Fu Y, Lentz TL. Rabies virus entry at the neuromuscular junction in nerve-muscle cocultures[J]. Muscle Nerve,2000,23(5):720-730.
[15]
Langevin C, Jaaro H, Bressanelli S, et al. Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of the mammalian p75 neurotrophin receptor[J]. J Biol Chem,2002,277(40):37655-37662.
[16]
Hemachudha T, Ugolini G, Wacharapluesadee S, et al. Human rabies: neuropathogenesis, diagnosis, and management[J]. Lancet Neurol,2013,12(5):498-513.
[17]
Publication W. Rabies vaccines: WHO position paper--recommendations[J]. Vaccine,2010,28(44):7140-7142.
[18]
周航，李昱，陈瑞丰, 等. 狂犬病预防控制技术指南(2016版)[J]. 中华流行病学杂志,2016,37(2):139-163.
[19]
Bharti OK, Thakur B, Rao R. Wound-only injection of rabies immunoglobulin (RIG) saves lives and costs less than a dollar per patient by "pooling strategy" [J]. Vaccine,2019,371:A128-A131.
[20]
Benmansour A, Leblois H, Coulon P, et al. Antigenicity of rabies virus glycoprotein[J]. J Virol,1991,65(8):4198-4203.
[21]
Lafon M, Wiktor TJ, Macfarlan RI. Antigenic sites on the CVS rabies virus glycoprotein: analysis with monoclonal antibodies[J]. J Gen Virol,1983,64(Pt 4):843-851.
[22]
Goudsmit J, Marissen WE, Weldon WC, et al. Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin[J]. J Infect Dis,2006,193(6):796-801.
[23]
Kim PK, Ahn JS, Kim CM, et al. A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis[J]. PLoS One,2021,16(e02567799): e256779.
[24]
Both L, van Dolleweerd C, Wright E, et al. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans[J]. FASEB J,2013,27(5):2055-2065.
[25]
Safdari Y, Farajnia S, Asgharzadeh M, et al. Antibody humanization methods--a review and update[J]. Biotechnol Genet Eng Rev, 2013,29:175-86.
[26]
Chen C, Li N, Zhao Y, et al. Coupling recombinase-mediated cassette exchange with somatic hypermutation for antibody affinity maturation in CHO cells[J]. Biotechnol Bioeng,2016,113(1):39-51.
[27]
Green LL. Transgenic mouse strains as platforms for the successful discovery and development of human therapeutic monoclonal antibodies[J]. Curr Drug Discov Technol,2014,11(1):74-84.
[28]
Tiller T. Single B cell antibody technologies[J]. N Biotechnol, 2011,28(5):453-457.
[29]
Chao TY, Ren S, Shen E, et al. SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies[J]. PLoS Negl Trop Dis,2017,11(12):e6133.
[30]
Mcclain JB, Chuang A, Reid C, et al. Rabies virus neutralizing activity, pharmacokinetics, and safety of the monoclonal antibody mixture SYN023 in combination with rabies vaccination: Results of a phase 2, randomized, blinded, controlled trial[J]. Vaccine, 2021,39(40):5822-5830.
[31]
Wiktor TJ, Lerner RA, Koprowski H. Inhibitory effect of passive antibody on active immunity induced against rabies by vaccination[J]. Bull World Health Organ,1971,45(6):747-753.
[32]
李振平，王玉琳，刘燕, 等. 人狂犬病免疫球蛋白使用效果观察[J]. 微生物学免疫学进展,2004,32(2):32-34.
[33]
Lang J, Simanjuntak GH, Soerjosembodo S, et al. Suppressant effect of human or equine rabies immunoglobulins on the immunogenicity of post-exposure rabies vaccination under the 2-1-1 regimen: a field trial in Indonesia. MAS054 Clinical Investigator Group[J]. Bull World Health Organ,1998,76(5):491-495.
[34]
Vodopija I, Sureau P, Smerdel S, et al. Interaction of rabies vaccine with human rabies immunoglobulin and reliability of a 2-1-1 schedule application for postexposure treatment[J]. Vaccine,1988,6(3):283-286.
[35]
Nicholson KG, Turner GS. Studies with human diploid cell strain rabies vaccine and human antirabies immunoglobulin in man[J]. Dev Biol Stand,1978;40:115-120.
[36]
Saesow N, Chaiwatanarat T, Mitmoonpitak C, et al. Diffusion and fate of intramuscularly injected human rabies immune globulin[J]. Acta Trop,2000,76(3):289-292.
[37]
吕新军，申辛欣，唐青, 等. 改良抗体结合试验检测人用狂犬病疫苗效价方法的初步建立[J]. 中国疫苗和免疫,2014,20(3):250-253.
[38]
吴未辰，罗静霞，梁伟献, 等. 狂犬病免疫球蛋白应用研究进展[J]. 病毒学报,2016,32(5):666-670.
[39]
Bharti OK, Madhusudana SN, Wilde H. Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG[J]. Hum Vaccin Immunother,2017,13(4):762-765.
[40]
World Health Organization. WHO Expert Consultation on Rabies, third report[M]. Geneva: World Health Organization, 2018.
[41]
Madhusudana SN, Ashwin BY, Sudarshan S. Feasibility of reducing rabies immunoglobulin dosage for passive immunization against rabies results of in vitro and in vivo studies[J]. Hum Vaccin Immunother,2013,9(9):1914-1917.
[42]
殷文武，王传林，陈秋兰, 等. 狂犬病暴露预防处置专家共识[J]. 中华预防医学杂志,2019,53(7):668-679.
No related articles found!
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号