基于负链RNA病毒的自我复制载体
Self-replicating vehicles based on negative strand RNA viruses
原文发布日期:2022-02-15
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Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating RNA viral vectors, particularly oncolytic viruses, have been applied for cancer therapy and immunotherapy. Among negative strand RNA viruses, measles viruses and rhabdoviruses have been frequently applied for vaccine development against viruses such as Chikungunya virus, Lassa virus, Ebola virus, influenza virus, HIV, Zika virus, and coronaviruses. Immunization of rodents and primates has elicited strong neutralizing antibody responses and provided protection against lethal challenges with pathogenic viruses. Several clinical trials have been conducted. Ervebo, a vaccine based on a vesicular stomatitis virus (VSV) vector has been approved for immunization of humans against Ebola virus. Different types of cancers such as brain, breast, cervical, lung, leukemia/lymphoma, ovarian, prostate, pancreatic, and melanoma, have been the targets for cancer vaccine development, cancer gene therapy, and cancer immunotherapy. Administration of measles virus and VSV vectors have demonstrated immune responses, tumor regression, and tumor eradication in various animal models. A limited number of clinical trials have shown well-tolerated treatment, good safety profiles, and dose-dependent activity in cancer patients.
自复制RNA病毒已被改造为高效表达载体,用于传染病和癌症的疫苗研发。此外,自复制RNA病毒载体,特别是溶瘤病毒,已应用于癌症治疗和免疫治疗。在负链RNA病毒中,麻疹病毒和弹状病毒常被用于开发针对基孔肯雅病毒、拉沙病毒、埃博拉病毒、流感病毒、HIV、寨卡病毒和冠状病毒等的疫苗。啮齿动物和灵长类动物的免疫接种已引发强效中和抗体反应,并对致死性病原体攻击产生保护作用。目前已开展多项临床试验。基于水疱性口炎病毒(VSV)载体的Ervebo疫苗已获批准用于人类预防埃博拉病毒。脑癌、乳腺癌、宫颈癌、肺癌、白血病/淋巴瘤、卵巢癌、前列腺癌、胰腺癌和黑色素瘤等不同类型的癌症已成为癌症疫苗开发、癌症基因治疗和癌症免疫治疗的目标。麻疹病毒和VSV载体的应用在各种动物模型中展现出免疫反应、肿瘤消退和肿瘤清除的效果。少量临床试验显示,这些治疗方法在癌症患者中耐受性良好、安全性高,并具有剂量依赖性活性。
Self-replicating vehicles based on negative strand RNA viruses
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