Huang Fei, Ren Meishen, Pei Jie, Mei Hong, Sui Baokun, Wu Qiong, Chai Benjie, Yang Ruicheng, Zhou Ming, Fu Zhen F, Zhou Huiping, Zhao Ling
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Front Microbiol. 2021 Aug 19;12:702273. doi: 10.3389/fmicb.2021.702273. eCollection 2021.
Rabies, a fatal disease in humans and other mammals, is caused by the rabies virus (RABV), and it poses a public health threat in many parts of the world. Once symptoms of rabies appear, the mortality is near 100%. There is currently no effective treatment for rabies. In our study, two human-derived RABV-neutralizing antibodies (RVNA), CR57 and CR4098, were cloned into adeno-associated virus (AAV) vectors, and recombinant AAVs expressing RVNA were evaluated for postexposure prophylaxis after intrathecal injection into RABV-infected rats. At 4days post-infection with a lethal dose of RABV, 60% of the rats that received an intrathecal injection of AAV-CR57 survived, while 100% of the rats inoculated with AAV-enhanced green fluorescent protein (EGFP) succumbed to rabies. Overall, these results demonstrate that AAV-encoding RVNA can be utilized as a potential human rabies postexposure prophylaxis.
狂犬病是一种在人类和其他哺乳动物中致死的疾病，由狂犬病病毒（RABV）引起，在世界许多地区构成公共卫生威胁。一旦狂犬病症状出现，死亡率接近100%。目前尚无有效的狂犬病治疗方法。在我们的研究中，将两种人源狂犬病病毒中和抗体（RVNA）CR57和CR4098克隆到腺相关病毒（AAV）载体中，并对表达RVNA的重组腺相关病毒经鞘内注射到感染狂犬病病毒的大鼠体内后进行暴露后预防评估。在感染致死剂量狂犬病病毒4天后，接受鞘内注射AAV-CR57的大鼠中有60%存活，而接种AAV-增强型绿色荧光蛋白（EGFP）的大鼠100%死于狂犬病。总体而言，这些结果表明，编码RVNA的腺相关病毒可作为潜在的人类狂犬病暴露后预防手段。
