Nouscom srl, Via di Castel Romano 100, 00128 Rome, Italy; Ceinge-Biotecnologie Avanzate S.C. A.R.L., via Gaetano Salvatore 486, 80145 Naples, Italy.
Nouscom srl, Via di Castel Romano 100, 00128 Rome, Italy.
Semin Immunol. 2020 Aug;50:101430. doi: 10.1016/j.smim.2020.101430. Epub 2020 Nov 29.
Since the discovery in 1796 by Edward Jenner of vaccinia virus as a way to prevent and finally eradicate smallpox, the concept of using a virus to fight another virus has evolved into the current approaches of viral vectored genetic vaccines. In recent years, key improvements to the vaccinia virus leading to a safer version (Modified Vaccinia Ankara, MVA) and the discovery that some viruses can be used as carriers of heterologous genes encoding for pathological antigens of other infectious agents (the concept of 'viral vectors') has spurred a new wave of clinical research potentially providing for a solution for the long sought after vaccines against major diseases such as HIV, TB, RSV and Malaria, or emerging infectious diseases including those caused by filoviruses and coronaviruses. The unique ability of some of these viral vectors to stimulate the cellular arm of the immune response and, most importantly, T lymphocytes with cell killing activity, has also reawakened the interest toward developing therapeutic vaccines against chronic infectious diseases and cancer. To this end, existing vectors such as those based on Adenoviruses have been improved in immunogenicity and efficacy. Along the same line, new vectors that exploit viruses such as Vesicular Stomatitis Virus (VSV), Measles Virus (MV), Lymphocytic choriomeningitis virus (LCMV), cytomegalovirus (CMV), and Herpes Simplex Virus (HSV), have emerged. Furthermore, technological progress toward modifying their genome to render some of these vectors incompetent for replication has increased confidence toward their use in infant and elderly populations. Lastly, their production process being the same for every product has made viral vectored vaccines the technology of choice for rapid development of vaccines against emerging diseases and for 'personalised' cancer vaccines where there is an absolute need to reduce time to the patient from months to weeks or days. Here we review the recent developments in viral vector technologies, focusing on novel vectors based on primate derived Adenoviruses and Poxviruses, Rhabdoviruses, Paramixoviruses, Arenaviruses and Herpesviruses. We describe the rationale for, immunologic mechanisms involved in, and design of viral vectored gene vaccines under development and discuss the potential utility of these novel genetic vaccine approaches in eliciting protection against infectious diseases and cancer.
自 1796 年爱德华·詹纳发现牛痘病毒可预防天花并最终根除天花以来，利用病毒对抗另一种病毒的概念已发展成为当前的病毒载体基因疫苗方法。近年来，对导致更安全版本（改良安卡拉牛痘病毒，MVA）的牛痘病毒的关键改进以及发现某些病毒可用作编码其他传染性病原体病理性抗原的异源基因载体（“病毒载体”的概念），激发了新的临床研究浪潮，为长期寻求针对艾滋病病毒、结核病、呼吸道合胞病毒和疟疾等主要疾病或包括丝状病毒和冠状病毒在内的新兴传染病的疫苗提供了潜在解决方案。其中一些病毒载体刺激细胞免疫反应的独特能力，最重要的是具有细胞杀伤活性的 T 淋巴细胞，也重新唤起了开发针对慢性传染病和癌症的治疗性疫苗的兴趣。为此，已经改进了现有的基于腺病毒的载体，以提高其免疫原性和功效。沿着同样的思路，已经出现了利用水疱性口炎病毒（VSV）、麻疹病毒（MV）、淋巴细胞性脉络丛脑膜炎病毒（LCMV）、巨细胞病毒（CMV）和单纯疱疹病毒（HSV）等病毒的新型载体。此外，朝着修饰其基因组以使其中一些载体失去复制能力的技术进步提高了对在婴儿和老年人群中使用这些载体的信心。最后，由于它们的生产过程对每种产品都是相同的，因此病毒载体疫苗已成为针对新兴疾病和“个性化”癌症疫苗快速开发的首选技术，在这些疫苗中，从数月到数周或数天的时间内将患者的需求减少到绝对必要。在这里，我们回顾了病毒载体技术的最新进展，重点介绍了基于灵长类衍生的腺病毒和痘病毒、弹状病毒、副粘病毒、沙粒病毒和疱疹病毒的新型载体。我们描述了正在开发的病毒载体基因疫苗的基本原理、所涉及的免疫机制和设计，并讨论了这些新型遗传疫苗方法在引发针对传染病和癌症的保护方面的潜在应用。
