Abdel Malak Camelia A, Abelhafez Tawfeek H, Tabll Ashraf A, Mashaly Mohammad M, El Shenawy Reem, El-Abd Yasmine S, Shaker Maysa H, El-Awady Mostafa K
Department of Chemistry, Faculty of Science, Damietta University, Damietta, Egypt.
Department of Microbial Biotechnology, National Research Center, Giza, Egypt.
Hum Antibodies. 2017;26(3):127-134. doi: 10.3233/HAB-170330.
Assessment of the neutralizing activity of human monoclonal antibodies against HCV and also study their safety in experimental small animals (Swiss mice).
Assessment of neutralizing activity of human monoclonal antibodies against HCV envelope regions (E1, E2) by two methods: by HCV cc infectious system 1) and by using positive HCV positive serum as source of HCV particles genotype 4a (neutralizing assay 2). Dot ELISA was used to study the activity of the generated antibodies. Safety and toxicity of the generated human antibodies were tested by assessing the changes in the biochemistry of liver function and kidney function tests, Complete blood counts (CBC) and studying the pathological changes with different concentrations of purified human antibodies were carried out..
Human Abs # 5 & 11 showed neutralizing activity by (neutralizing assay 2) but were not neutralizing by HCV cc assay. Human Abs # 12 & 15 showed neutralizing activity by the two methods i.e our generated human antibodies Abs# 5 &11 & 12 & 15 were neutralizing for HCV genotype 4a and Abs # 12 & 15 were neutralizing for HCV genotypes 4a and 2a. Liver and kidney functions and CBC results indicated that doses of 10 μg, 100 μg were safe. The histopathological results indicated that the dose of 10 μg of purified human monoclonal antibodies per mouse body weight was safe.
The generated human monoclonal antibodies can be used to develop potent immunotherapy agents that can be administrated for the post-transplantation patients to prevent the recurrence of HCV infection. Also, the monoclonal antibodies can be used to develop a candidate vaccine against HCV.
评估人源单克隆抗体对丙型肝炎病毒（HCV）的中和活性，并研究其在实验性小动物（瑞士小鼠）中的安全性。
通过两种方法评估人源单克隆抗体对HCV包膜区域（E1、E2）的中和活性：1）通过HCV细胞培养感染性系统；2）使用HCV阳性血清作为4a型HCV颗粒的来源（中和试验2）。采用斑点酶联免疫吸附测定法（Dot ELISA）研究产生的抗体活性。通过评估肝功能和肾功能生化指标的变化、全血细胞计数（CBC）以及研究不同浓度纯化人源抗体的病理变化来测试所产生的人源抗体的安全性和毒性。
人源抗体#5和#11通过（中和试验2）显示出中和活性，但通过HCV细胞培养感染性系统试验未表现出中和活性。人源抗体#12和#15通过两种方法均显示出中和活性，即我们所产生的人源抗体#5、#11、#12和#15对4a型HCV具有中和作用，抗体#12和#15对4a型和2a型HCV均具有中和作用。肝脏和肾脏功能以及全血细胞计数结果表明，10μg、100μg的剂量是安全的。组织病理学结果表明，每只小鼠体重10μg纯化人源单克隆抗体的剂量是安全的。
所产生的人源单克隆抗体可用于开发有效的免疫治疗药物，用于移植后患者以预防HCV感染复发。此外，单克隆抗体可用于开发抗HCV候选疫苗。
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