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痘病毒启动子增强 MVA 传递疫苗的免疫原性。

Poxviral promoters for improving the immunogenicity of MVA delivered vaccines.

机构信息

a Infectious Disease Research Department , King Abdullah International Medical Research Center (KAIMRC) , Riyadh , Saudi Arabia.

出版信息

Hum Vaccin Immunother. 2019;15(1):203-209. doi: 10.1080/21645515.2018.1513439. Epub 2018 Sep 6.

Abstract

Modified vaccinia virus Ankara (MVA) is a replication-deficient poxvirus, attenuated in chick embryo fibroblast primary cells. It has been utilised as a viral vector to develop many vaccines against cancer and infectious diseases such as malaria, HIV/AIDS, influenza, and tuberculosis, MERS-CoV, and Ebola virus infection. There is accumulating data from many preclinical and clinical studies that highlights the excellent safety and immunogenicity of MVA. However, due to the complex nature of many pathogens and their pathogenicity, MVA vectored vaccine candidates need to be optimised to improve their immunogenicity. One of the main approaches to improve MVA immunogenicity focuses on optimising poxviral promoters that drive recombinant vaccine antigens, encoded within recombinant MVA vector genome. A number of promoters were described or optimised to improve the development of MVA based vaccines such as p7.5, pF11, and mH5 promoters. This review focuses on poxviral promoters, their optimisation, genetic stability, and clinical use.

摘要

改良安卡拉痘苗病毒(MVA)是一种复制缺陷的痘病毒,在鸡胚成纤维原代细胞中被减弱。它已被用作病毒载体来开发针对癌症和传染病的许多疫苗,如疟疾、HIV/AIDS、流感和结核病、中东呼吸综合征冠状病毒和埃博拉病毒感染。越来越多的临床前和临床研究数据强调了 MVA 的出色安全性和免疫原性。然而,由于许多病原体的复杂性及其致病性,需要对 MVA 载体疫苗候选物进行优化以提高其免疫原性。提高 MVA 免疫原性的主要方法之一是优化驱动重组 MVA 载体基因组中编码的重组疫苗抗原的痘病毒启动子。已经描述或优化了许多启动子来改进基于 MVA 的疫苗的开发,如 p7.5、pF11 和 mH5 启动子。本文重点介绍痘病毒启动子及其优化、遗传稳定性和临床应用。

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