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The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector.
Molecular Biology ( IF 1.2 ) Pub Date : 2020-09-04 , DOI: 10.1134/s0026893320060151
T A Zaichuk 1 , Y D Nechipurenko 2 , A A Adzhubey 2, 3 , S B Onikienko 4 , V A Chereshnev 5 , S S Zainutdinov 6 , G V Kochneva 6 , S V Netesov 7 , O V Matveeva 1, 8
Affiliation  

Abstract

To design an effective and safe vaccine against betacoronaviruses, it is necessary to use their evolutionarily conservative antigenic determinants that will elicit the combination of strong humoral and cell-mediated immune responses. Targeting such determinants minimizes the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. Using more conservative structural and accessory viral proteins for the vaccine antigenic determinants will help to avoid this problem. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection.



中文翻译:

Betacoronaviruses 疫苗开发的挑战:抗体依赖性增强和仙台病毒作为可能的疫苗载体。

摘要

为了设计一种有效且安全的针对 β 冠状病毒的疫苗,有必要使用其进化上保守的抗原决定簇,从而引发强烈的体液和细胞介导的免疫反应。靶向此类决定因素可最大限度地降低抗体依赖性增强病毒感染的风险。这种现象在针对 SARS-CoV-1 和 MERS-CoV 的实验性疫苗的动物试验中观察到,这些疫苗是基于灭活的冠状病毒或表达病毒体刺突蛋白 (S) 的载体构建体开发的。S 蛋白抗原决定簇中某些氨基酸的取代和糖基化,以及其构象变化,可以在针对 SARS-CoV-2 的新实验疫苗中产生相同的效果。使用更保守的结构和辅助病毒蛋白作为疫苗抗原决定簇将有助于避免这个问题。这篇综述概述了开发基于非致病性病毒载体的新型 SARS-CoV-2 冠状病毒疫苗的方法。为了有效预防由呼吸道病原体引起的感染,疫苗刺激呼吸道粘膜免疫的能力很重要。这种疫苗可以使用非致病性仙台病毒载体开发,因为它可以鼻内给药并诱导粘膜免疫反应,从而增强呼吸道的抗病毒屏障并提供可靠的抗感染保护。这篇综述概述了开发基于非致病性病毒载体的新型 SARS-CoV-2 冠状病毒疫苗的方法。为了有效预防由呼吸道病原体引起的感染,疫苗刺激呼吸道粘膜免疫的能力很重要。这种疫苗可以使用非致病性仙台病毒载体开发,因为它可以鼻内给药并诱导粘膜免疫反应,从而增强呼吸道的抗病毒屏障并提供可靠的抗感染保护。这篇综述概述了开发基于非致病性病毒载体的新型 SARS-CoV-2 冠状病毒疫苗的方法。为了有效预防由呼吸道病原体引起的感染,疫苗刺激呼吸道粘膜免疫的能力很重要。这种疫苗可以使用非致病性仙台病毒载体开发,因为它可以鼻内给药并诱导粘膜免疫反应,从而增强呼吸道的抗病毒屏障并提供可靠的抗感染保护。

更新日期:2020-09-05
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