Zaichuk T A, Nechipurenko Y D, Adzhubey A A, Onikienko S B, Chereshnev V A, Zainutdinov S S, Kochneva G V, Netesov S V, Matveeva O V
Sendai Viralytics, Acton, MA, 117261 USA.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Mol Biol (Mosk). 2020 Nov-Dec;54(6):922-938. doi: 10.31857/S0026898420060154.
To design an effective and safe vaccine against betacoronaviruses, it is necessary to elicit a combination of strong humoral and cell-mediated immune responses as well as to minimize 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. 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. The mucosal immunity and the production of IgA antibodies accompanying its development reduces the likelihood of developing an antibody-dependent infection enhancement, which is usually associated only with immunopathological IgG antibodies.
为设计一种针对β冠状病毒的有效且安全的疫苗,有必要引发强烈的体液免疫和细胞介导免疫反应的组合,同时将病毒感染的抗体依赖性增强风险降至最低。在基于灭活冠状病毒或表达病毒粒子刺突蛋白(S)的载体构建体开发的针对SARS-CoV-1和MERS-CoV的实验性疫苗的动物试验中观察到了这种现象。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,在针对SARS-CoV-2的新实验性疫苗中可能会导致相同的效果。本综述概述了基于非致病性病毒载体开发针对新型SARS-CoV-2冠状病毒疫苗的方法。为有效预防呼吸道病原体引起的感染,疫苗刺激呼吸道黏膜免疫的能力很重要。可以使用非致病性仙台病毒载体开发这样的疫苗,因为它可以通过鼻内给药并诱导黏膜免疫反应,加强呼吸道中的抗病毒屏障并提供可靠的抗感染保护。黏膜免疫及其伴随产生的IgA抗体降低了发生抗体依赖性感染增强的可能性,而这种增强通常仅与免疫病理IgG抗体相关。