Karimi Sahar, Nazarian Shahram, Sotoodehnejadnematalahi Fattah, Dorostkar Roohollah, Amani Jafar
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, Imam Hossein University, Tehran, Iran.
Iran J Pharm Res. 2023 Sep 10;22(1):e137751. doi: 10.5812/ijpr-137751. eCollection 2023 Jan-Dec.
Since December 2019, the world has been grappling with an ongoing global COVID-19 pandemic. Various virus variants have emerged over the past two years, each posing a greater threat than its predecessors. The recent appearance of the omicron variant (B.1.1.529) has raised significant alarm within the field of epidemiology due to its highly contagious nature and rapid transmission rate. The omicron variant possessed mutations in the key receptor-binding domain (RBD) region, the S region, and these modifications have shown a notable impact on the strain's susceptibility to neutralizing antibodies. Developing safe and efficient vaccines to prevent a future severe acute respiratory outbreak of coronavirus syndrome 2 (SARS-CoV-2) is significant. Viral surface spike proteins are ideal targets for vaccines. This study aimed to find a multi-subunit chimeric vaccine. After conducting bioinformatics analysis, the recombinant spike (RS) protein of SARS-CoV-2 was deliberately designed and subsequently produced using expression systems. The immunogenicity of RS and neutralizing antibody responses were evaluated on immunized BALB/c mice. There was a significant difference in antibody titers between RS-immunized mice and control groups. The endpoint of the serum antibody titer of mice immunized with our chimeric protein was 2.5 times higher than that of the negative control. The chimeric construct could present multiple antigens simultaneously, influentially affecting immunization. Sera from mice vaccinated by RS could recognize the SARS-CoV-2 virus and neutralize antibodies. Our chimeric peptide could bind to antibodies in the serum of patients infected with different serotypes of the SARS-CoV-2 virus, such as alpha, delta, and omicron variants. The results indicated that the RS protein would be a potential novel antigenic candidate for subunit vaccine development and could be used as a useful alternative to generate diagnostic serological tests for SARS-CoV-2 infection.
自2019年12月以来，全球一直在应对持续的新冠疫情。在过去两年中出现了各种病毒变种，每一种都比其前身构成更大的威胁。最近出现的奥密克戎变种（B.1.1.529）因其高度传染性和快速传播率，在流行病学领域引起了极大恐慌。奥密克戎变种在关键的受体结合域（RBD）区域、S区域存在突变，这些修饰对该毒株对中和抗体的敏感性产生了显著影响。研发安全有效的疫苗以预防未来严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的爆发具有重要意义。病毒表面刺突蛋白是疫苗的理想靶点。本研究旨在寻找一种多亚基嵌合疫苗。在进行生物信息学分析后，特意设计了SARS-CoV-2的重组刺突（RS）蛋白，随后使用表达系统进行生产。在免疫的BALB/c小鼠上评估了RS的免疫原性和中和抗体反应。RS免疫小鼠与对照组之间的抗体滴度存在显著差异。用我们的嵌合蛋白免疫的小鼠血清抗体滴度终点比阴性对照高2.5倍。嵌合构建体可以同时呈现多种抗原，对免疫产生显著影响。RS疫苗接种小鼠的血清能够识别SARS-CoV-2病毒并中和抗体。我们的嵌合肽可以与感染不同血清型SARS-CoV-2病毒（如阿尔法、德尔塔和奥密克戎变种）患者血清中的抗体结合。结果表明，RS蛋白将是亚单位疫苗开发的潜在新型抗原候选物，可作为一种有用的替代物用于生成SARS-CoV-2感染的诊断血清学检测。
