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IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability
bioRxiv - Immunology Pub Date : 2020-05-21 , DOI: 10.1101/2020.05.21.108159
Yuan Zhang , Yanqiu Wei , Yunlong Li , Xuan Wang , Yang Liu , Deyu Tian , Xiaojuan Jia , Rui Gong , Wenjun Liu , Limin Yang

Ebola virus (EBOV) is the most virulent pathogens that cause hemorrhagic fever with high mortality rates in humans and nonhuman primates. The postexposure antibody therapies to prevent EBOV infection are considered efficient. However, due to the poor thermal stability of mammalian antibody, their application in the tropics has been limited. Here, we developed a thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25°C for one year, in contrast to conventional polyclonal or monoclonal antibodies (MAbs). We immunized laying hens with a variety of EBOV vaccine candidates and confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralizing antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice model. Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralizing antibody units/kilogram) achieved complete protection with no signs of disease, while the low-dose group was only partially protected. In contrast, all mice receiving naïve IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy, and it is very promising to be developed as alternative therapeutic entities.

中文翻译:

抗埃博拉病毒的IgY抗体具有暴露后保护和出色的热稳定性

埃博拉病毒(EBOV)是最致命的病原体,可引起人类和非人类灵长类动物出血热,死亡率很高。预防EBOV感染的暴露后抗体疗法被认为是有效的。但是,由于哺乳动物抗体的热稳定性差,因此它们在热带地区的应用受到限制。在这里,我们开发了基于鸡免疫球蛋白Y(IgY)的针对EBOV的热稳定治疗性抗体。与传统的多克隆或单克隆抗体(MAbs)相比,IgY抗体具有出色的热稳定性,在25°C的温度下可保持一年的中和活性。我们用多种EBOV候选疫苗免疫了蛋鸡,并确认编码EBOV糖蛋白的VSVΔG/ EBOVGP可以诱导针对EBOV的高滴度中和抗体。在新生的Balb / c小鼠模型中评估了免疫IgY抗体在体内的治疗效果。感染后2或24小时,用不同剂量的抗EBOV IgY治疗致死剂量的病毒攻击小鼠。接受106 NAU / kg高剂量的组(中和抗体单位/千克)获得了完全保护,没有疾病迹象,而低剂量组仅得到了部分保护。相反,所有接受初次IgY的小鼠在10天内死亡。总之,抗EBOV IgY表现出优异的热稳定性和保护功效,非常有希望将其开发为替代治疗实体。接受106 NAU / kg高剂量的组(中和抗体单位/千克)获得了完全保护,没有疾病迹象,而低剂量组仅得到了部分保护。相反,所有接受初次IgY的小鼠在10天内死亡。总之,抗EBOV IgY表现出优异的热稳定性和保护功效,非常有希望将其开发为替代治疗实体。接受106 NAU / kg高剂量的组(中和抗体单位/千克)获得了完全保护,没有疾病迹象,而低剂量组仅得到了部分保护。相反,所有接受初次IgY的小鼠在10天内死亡。总之,抗EBOV IgY表现出优异的热稳定性和保护功效,非常有希望将其开发为替代治疗实体。
更新日期:2020-05-21
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