论文部分内容阅读
本研究对重组人源抗狂犬病毒单克隆抗体鸡尾酒暴露后预防效果进行评价,选用狂犬病毒国内代表性疫苗株、实验室固定毒株及街毒株共11株病毒,通过荧光抗体病毒中和试验(FAVN)分析针对狂犬病毒糖蛋白Ⅰ、Ⅱ、Ⅲ号表位的三株单抗CR57(I)、RV08(II)和RV3A5(Ⅲ)及其鸡尾酒配伍的中和谱,在此基础上选用狂犬病病毒标准攻击毒株CVS-11感染仓鼠腓肠肌,进一步研究重组人源抗狂犬病毒单抗及其鸡尾酒制剂暴露后保护效果,结果显示CR57、RV08、RV3A5及其三联配伍制剂对11株狂犬病毒均具有明确的中和作用,按中和效价1∶1∶1配伍组成的鸡尾酒组合制剂对这些毒株的中和能力没有减弱,表明三株抗体间无相互干扰,对个别毒株(JX08-45、Flury、SRV9)的中和活性表现出协同作用;三株单抗CR57、RV08和RV3A5单独应用或是三联配伍应用的暴露后保护率达100%,与HRIG单独免疫相比较具有更优秀的动物保护活性;在与疫苗联合应用方面重组人源单抗与HRIG在暴露后预防的效果相仿,均可达到100%的保护率,所以重组人源单抗具有替代HRIG应用于狂犬病暴露后预防与保护的潜力,为我国具有自主知识产权的狂犬单抗鸡尾酒制剂的研发打下基础。
In this study, we evaluated the prophylactic effect of recombinant human anti-rabies monoclonal antibody cocktail after exposure. We selected 11 strains of rabies virus domestic representative vaccine strains, laboratory-fixed strains and street-strain strains and passed the fluorescent antibody virus neutralization test (FAVN) was used to analyze the neutralization spectrum of three McAbs CR57 (I), RV08 (II) and RV3A5 (Ⅲ) and their cocktails targeting rabies glycoprotein Ⅰ, Ⅱ and Ⅲ epitopes. On this basis, The rabies virus standard challenge strain CVS-11 was infected with hamster gastrocnemius to further study the protective effect of recombinant human anti-rabies monoclonal antibody and its cocktail formulation after exposure. The results showed that CR57, RV08, RV3A5 and their triple compatibility formulations Has a clear neutralization effect. The neutralizing ability of these cocktail strains did not weaken when the neutralizing potency 1: 1: 1 neutralizing cocktail composition showed that the three antibodies did not interfere with each other, and the individual strains (JX08- 45, Flury and SRV9) showed synergistic effect. The protection rates of three McAbs CR57, RV08 and RV3A5 alone or in combination with three groups were 100% after exposure, which was better than that of HRIG alone Show the animal protection activity; in combination with the vaccine recombinant human monoclonal antibody and HRIG post-exposure prevention effect similar to 100% protection rate can be achieved, so the recombinant human monoclonal antibody with HRIG application after rabies exposure Prevention and protection of the potential for our country with independent intellectual property rights of rabies monoclonal antibody cocktail preparation lay the foundation.