Abstract

Flaviviruses, the viruses in the Flavivirus genus, Flaviviridae family, cause diseases with varying degrees of severity in human beings, including fevers (Yellow fever, Dengue fever, West Nile fever, Zika fever, etc.) and encephalites (tick-borne encephalitis, Japanese encephalitis, Powassan encephalitis, etc.). Preventive vaccines have been produced against only some of these infectious agents, with their development being mainly hindered by the neurovirulence of flaviviruses, as well as by a long-known phenomenon, namely, the antibody-dependent enhancement (ADE) of infection characteristic of these viruses. The use of serum therapy in the case of flaviviruses has several limitations. Donor blood. which serves as a raw material to obtain specific immunoglobulins, is always a limited resource, and different blood samples are not standardized by the level of protective antibodies they contain. The risk of ADE is also a significant limitation. A number of technologies are currently available that allow searching for antibodies with desired biological characteristics, such as high efficiency and broad neutralization ability with no ADE induction. This paper discusses the monoclonal antibodies obtained using cell engineering techniques including hybridoma mouse, recombinant chimeric (humanized) mouse/human or primate/human, and recombinant wholly human antibodies, which are currently studied in vitro and in vivo as potential therapeutic agents inhibiting the entry of flaviviruses into sensitive host cells and/or restricting their replication.

中文翻译：

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利用黄病毒特异性单克隆抗体研究黄病毒的抗原结构并开发抗黄病毒药物

摘要

黄病毒，黄病毒中的病毒黄病毒科属，引起人类不同程度的疾病，包括发烧（黄热病、登革热、西尼罗热、寨卡热等）和脑炎（蜱传脑炎、日本脑炎、波瓦桑脑炎等） .) 仅针对这些传染源中的一些生产了预防性疫苗，它们的发展主要受到黄病毒的神经毒力以及一个众所周知的现象的阻碍，即这些感染特征的抗体依赖性增强 (ADE)病毒。在黄病毒的情况下使用血清疗法有几个限制。献血者。作为获得特定免疫球蛋白的原料，它始终是一种有限的资源，不同的血液样本并没有根据它们所含保护性抗体的水平进行标准化。ADE 的风险也是一个重要的限制。目前有许多技术可以用于寻找具有所需生物学特性的抗体，例如高效和广泛的中和能力，无需 ADE 诱导。本文讨论了使用细胞工程技术获得的单克隆抗体，包括杂交瘤小鼠、重组嵌合（人源化）小鼠/人或灵长类动物/人，以及重组全人抗体，这些抗体目前在体外和体内研究作为潜在的治疗药物进入黄病毒进入敏感宿主细胞和/或限制它们的复制。目前有许多技术可以用于寻找具有所需生物学特性的抗体，例如高效和广泛的中和能力，无需 ADE 诱导。本文讨论了使用细胞工程技术获得的单克隆抗体，包括杂交瘤小鼠、重组嵌合（人源化）小鼠/人或灵长类动物/人，以及重组全人抗体，目前在体外和体内研究这些抗体作为抑制进入的潜在治疗剂。黄病毒进入敏感宿主细胞和/或限制它们的复制。目前有许多技术可以用于寻找具有所需生物学特性的抗体，例如高效和广泛的中和能力，无需 ADE 诱导。本文讨论了使用细胞工程技术获得的单克隆抗体，包括杂交瘤小鼠、重组嵌合（人源化）小鼠/人或灵长类动物/人，以及重组全人抗体，目前在体外和体内研究这些抗体作为抑制进入的潜在治疗剂。黄病毒进入敏感宿主细胞和/或限制它们的复制。