在COVID-19大流行期间,SARS-CoV-2减毒活疫苗受到的关注相对较少。尽管如此,获得减毒冠状病毒的几种方法是已知的。在这次系统审查中,冠状病毒减毒的策略,确定了可能应用于SARS-CoV-2的方法。PubMed,Scopus,搜索WebofScience和Embase数据库以鉴定描述体内测试的减毒突变的相关文章。在SARS-CoV-2以外的冠状病毒的情况下,序列比对用于排除不能应用于SARS-CoV-2的减毒突变。潜在的免疫原性,基于动物研究数据讨论了SARS-CoV-2减毒疫苗的安全性和有效性.总共有27种衰减策略,用来制造101种不同的冠状病毒,已在56篇符合条件的文章中进行了描述。SARS-CoV-2刺突蛋白中弗林蛋白酶切割位点的破坏被认为是最有希望的策略。转录调控信号的核心序列的置换,防止与野生型病毒重组,也显得特别有利。其他重要的减毒突变主要包括预防先天免疫的逃避。充分减毒的冠状病毒通常不会在易感动物中引起有意义的疾病,并保护它们免受毒性病毒的攻击。这表明减毒的COVID-19疫苗可能被认为是对抗SARS-CoV-2威胁的潜在策略。
Live-attenuated SARS-CoV-2 vaccines received relatively little attention during the COVID-19 pandemic. Despite this, several methods of obtaining attenuated coronaviruses are known. In this systematic
review, the strategies of coronavirus attenuation, which may potentially be applied to SARS-CoV-2, were identified. PubMed, Scopus, Web of Science and Embase databases were searched to identify relevant articles describing attenuating mutations tested in vivo. In case of coronaviruses other than SARS-CoV-2, sequence alignment was used to exclude attenuating mutations that cannot be applied to SARS-CoV-2. Potential immunogenicity, safety and efficacy of the attenuated SARS-CoV-2 vaccine were discussed based on animal studies data. A total of 27 attenuation strategies, used to create 101 different coronaviruses, have been described in 56 eligible articles. The disruption of the furin cleavage site in the SARS-CoV-2 spike protein was identified as the most promising strategy. The replacement of core sequences of transcriptional regulatory signals, which prevents recombination with wild-type viruses, also appears particularly advantageous. Other important attenuating mutations encompassed mostly the prevention of evasion of innate immunity. Sufficiently attenuated coronaviruses typically caused no meaningful disease in susceptible animals and protected them from challenges with virulent virus. This indicates that attenuated COVID-19 vaccines may be considered as a potential strategy to fight the threat posed by SARS-CoV-2.