Sahin Fikret, Atasoy Buse Turegun, Yalcin Suleyman, Bitirim Verda Ceylan
Department of Medical Microbiology, University of Ankara, Ankara, 06100, Turkey.
Faculty of Medicine, Department of Medical Microbiology, Ankara University, Morphology Building, Sihhiye, Ankara, 06100, Turkey.
Sci Rep. 2025 Mar 29;15(1):10899. doi: 10.1038/s41598-025-95503-y.
The COVID-19 pandemic has underscored the urgent need for a vaccine strategy that is safe, effective, rapid, cost-efficient, and scalable for large-scale deployment during widespread infectious outbreaks. Here, we present a new vaccination strategy that meets these critical requirements. The SARS-CoV-2 S protein consists of the S1 and S2 subunits. The S2 subunit acts as the viral cell membrane fusion protein, and mutations in its C-terminal region facilitate the transport of the entire S protein to the cell membrane. When we expressed the SARS-CoV-2 S protein with a deletion of 21 amino acids from its C-terminal region in various cell types, we observed a dense presence of the protein in the cell membrane, as determined by IHC, dot blot, and ELISA. In the cell membrane-SARS-CoV-2 S protein complex, the cell membrane functions as an exosome mimic, carrying protein antigens (S protein) in their most natural form, as no further protocols are used to attach antigens to the membrane. We demonstrate that using the membrane-S protein component as a vaccine yields a more robust and protective immune response, with enhanced safety compared to mRNA-based or inactivated virus-based vaccines against SARS-CoV-2. Additionally, we show that fusing the transmembrane domain of the Vesicular Stomatitis Virus (VSV) G protein with the SARS-CoV-2 S1 protein effectively transports the S1 protein to the cell membrane, similar to SARS-CoV-2 S Δ21. We propose that designing the S2 subunit of the SARS-CoV-2 S protein, or its analogues such as the VSV-G protein, as carriers for fusing bacterial, viral, or tumor proteins with antigenic properties-and transporting them to the cell membrane-could result in a comprehensive vaccination protocol applicable to all bacteria, viruses, and even tumors.
新冠疫情凸显了制定疫苗策略的迫切需求，该策略应具备安全性、有效性、快速性、成本效益以及在广泛传染性疫情期间进行大规模部署的可扩展性。在此，我们提出一种满足这些关键要求的新疫苗接种策略。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突（S）蛋白由S1和S2亚基组成。S2亚基作为病毒细胞膜融合蛋白，其C末端区域的突变有助于整个S蛋白转运至细胞膜。当我们在多种细胞类型中表达C末端区域缺失21个氨基酸的SARS-CoV-2 S蛋白时，通过免疫组化（IHC）、斑点印迹和酶联免疫吸附测定（ELISA）确定，我们观察到该蛋白在细胞膜中大量存在。在细胞膜-SARS-CoV-2 S蛋白复合物中，细胞膜起到外泌体模拟物的作用，以其最天然的形式携带蛋白抗原（S蛋白），因为无需进一步的方案将抗原附着于膜上。我们证明，使用膜-S蛋白组分作为疫苗可产生更强有力和更具保护性的免疫反应，与基于信使核糖核酸（mRNA）或基于灭活病毒的针对SARS-CoV-2的疫苗相比，安全性有所提高。此外，我们表明，将水泡性口炎病毒（VSV）G蛋白的跨膜结构域与SARS-CoV-2 S1蛋白融合可有效地将S1蛋白转运至细胞膜，类似于SARS-CoV-2 S Δ21。我们提出，将SARS-CoV-2 S蛋白的S2亚基或其类似物（如水疱性口炎病毒G蛋白）设计为用于融合具有抗原特性的细菌、病毒或肿瘤蛋白并将它们转运至细胞膜的载体，可能会产生适用于所有细菌、病毒乃至肿瘤的全面疫苗接种方案。
