Abstract：
The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna\'s response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.5 strains. This approach, while commendable, is unfeasible in light of rapidly emerging mutated viral strains. PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2024. Articles included focused on specific themes such as the clinical history of recombinant protein vaccine development against different diseases, including COVID-19, the production of recombinant protein vaccines using different host expression systems, aspects to consider in recombinant protein vaccine development, and overcoming problems associated with large-scale recombinant protein vaccine production. In silico approaches to identify conserved and immunogenic epitopes could provide broad protection against SARS-CoV-2 VOCs but require validation in animal models. The recombinant protein vaccine development platform has shown a successful history in clinical development. Recombinant protein vaccines incorporating conserved epitopes may utilize a number of expression systems, such as yeast (Saccharomyces cerevisiae), baculovirus-insect cells (Sf9 cells), and Escherichia coli (E. coli). Current multi-epitope subunit vaccines against SARS-CoV-2 utilizing synthetic peptides are unfeasible for large-scale immunizations. Recombinant protein vaccines based on conserved and immunogenic proteins produced using E. coli offer high production yields, convenient purification, and cost-effective production of large-scale vaccine quantities capable of protecting against the SARS-CoV-2 D614G strain and its VOCs.
摘要：
COVID-19大流行继续导致感染和死亡，可归因于SARS-CoV-2Omicron变体（VOC）。Moderna对当前SARS-CoV-2疫苗对Omicron的保护效力下降的反应是开发一种基于武汉和OmicronBA4/BA.5菌株的Spike（S）蛋白的二价加强疫苗。这种方法,虽然值得称赞，鉴于迅速出现的突变病毒株是不可行的。截至2024年1月，PubMed和GoogleScholar对同行评审论文进行了系统审查。文章集中于特定主题，例如针对不同疾病的重组蛋白疫苗开发的临床历史，包括COVID-19，使用不同的宿主表达系统生产重组蛋白疫苗，重组蛋白疫苗开发中需要考虑的方面，并克服与大规模重组蛋白疫苗生产相关的问题。鉴定保守和免疫原性表位的计算机方法可以提供针对SARS-CoV-2VOC的广泛保护，但需要在动物模型中进行验证。重组蛋白疫苗开发平台在临床开发中已显示出成功的历史。整合保守表位的重组蛋白疫苗可以利用许多表达系统，如酵母（酿酒酵母），杆状病毒昆虫细胞（Sf9细胞），和大肠杆菌(E.大肠杆菌）。目前利用合成肽的针对SARS-CoV-2的多表位亚单位疫苗对于大规模免疫是不可行的。基于使用大肠杆菌生产的保守和免疫原性蛋白的重组蛋白疫苗提供高产量。方便净化，以及具有成本效益的大规模疫苗生产，能够预防SARS-CoV-2D614G菌株及其VOCs。
