表达分泌 scFv 的活疫苗狂犬病病毒的特性，用于狂犬病的治疗。

Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies.

机构信息

Wildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UK.

Institute for Infection and Immunity, St. George's Hospital Medical School, University of London, London SW17 0RE, UK.

出版信息

Viruses. 2023 Jul 31;15(8):1674. doi: 10.3390/v15081674.

DOI:10.3390/v15081674

PMID:37632016

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10458464/

Abstract

Rabies virus (RABV) causes possibly the oldest disease and is responsible for an estimated >59,000 human fatalities/year. Post exposure prophylaxis (PEP), the administration of vaccine and rabies immunoglobulin, is a highly effective tool which is frequently unavailable in RABV endemic areas. Furthermore, due to the constraints of the blood-brain barrier, current PEP regimes are ineffective after the onset of clinical symptoms which invariably result in death. To circumvent this barrier, a live-attenuated recombinant RABV expressing a highly RABV-neutralising scFv antibody (62-71-3) linked to the fluorescent marker mCherry was designed. Once rescued, the resulting construct (named RABV-62scFv) was grown to high titres, its growth and cellular dissemination kinetics characterised, and the functionality of the recombinant 62-71-3 scFv assessed. Encouraging scFv production and subsequent virus neutralisation results demonstrate the potential for development of a therapeutic live-attenuated virus-based post-infection treatment (PIT) for RABV infection.

摘要

狂犬病病毒（RABV）可能导致最古老的疾病，每年估计导致>59000 人死亡。暴露后预防（PEP），即疫苗和狂犬病免疫球蛋白的接种，是一种非常有效的工具，但在 RABV 流行地区经常无法获得。此外，由于血脑屏障的限制，目前的 PEP 方案在出现临床症状后无效，而这些症状通常会导致死亡。为了规避这一障碍，设计了一种表达与荧光标记物 mCherry 相连的高度中和 RABV 的 scFv 抗体（62-71-3）的减毒重组 RABV。一旦被拯救，所得构建体（命名为 RABV-62scFv）被生长到高滴度，其生长和细胞传播动力学被表征，并评估了重组 62-71-3 scFv 的功能。令人鼓舞的 scFv 产生和随后的病毒中和结果表明，开发针对 RABV 感染的基于治疗性减毒病毒的感染后治疗（PIT）具有潜力。