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展示 SARS-CoV-2 刺突蛋白受体结合域的类病毒颗粒:一种基于 VLP 的潜在 COVID-19 疫苗。

Virus-like Particles of Nodavirus Displaying the Receptor Binding Domain of SARS-CoV-2 Spike Protein: A Potential VLP-Based COVID-19 Vaccine.

机构信息

Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM, Serdang 43400, Selangor, Malaysia.

Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM, Serdang 43400, Selangor, Malaysia.

出版信息

Int J Mol Sci. 2023 Feb 23;24(5):4398. doi: 10.3390/ijms24054398.

Abstract

Since the outbreak of the coronavirus disease 2019 (COVID-19), various vaccines have been developed for emergency use. The efficacy of the initial vaccines based on the ancestral strain of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has become a point of contention due to the emergence of new variants of concern (VOCs). Therefore, continuous innovation of new vaccines is required to target upcoming VOCs. The receptor binding domain (RBD) of the virus spike (S) glycoprotein has been extensively used in vaccine development due to its role in host cell attachment and penetration. In this study, the RBDs of the Beta (β) and Delta (δ) variants were fused to the truncated nodavirus capsid protein without the protruding domain (CΔ116-NV-CP). Immunization of BALB/c mice with the virus-like particles (VLPs) self-assembled from the recombinant CP showed that, with AddaVax as an adjuvant, a significantly high level of humoral response was elicited. Specifically, mice injected with equimolar of adjuvanted CΔ116-NV-CP fused with the RBD of the β- and δ-variants increased T helper (Th) cell production with a CD8/CD4 ratio of 0.42. This formulation also induced proliferation of macrophages and lymphocytes. Overall, this study demonstrated that the nodavirus truncated CP fused with the SARS-CoV-2 RBD has potential to be developed as a VLP-based COVID-19 vaccine.

摘要

自 2019 年冠状病毒病(COVID-19)爆发以来,已经开发出各种用于紧急使用的疫苗。由于新的关注变种(VOC)的出现,最初基于严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)的祖先株的疫苗的功效成为了争议的焦点。因此,需要不断创新针对即将出现的 VOC 的新疫苗。由于病毒刺突(S)糖蛋白的受体结合域(RBD)在宿主细胞附着和穿透中起作用,因此已广泛用于疫苗开发。在这项研究中,将β(β)和德尔塔(δ)变体的 RBD 融合到没有突出结构域(CΔ116-NV-CP)的截断的诺如病毒衣壳蛋白中。用自组装的重组 CP 病毒样颗粒(VLPs)免疫 BALB/c 小鼠表明,用 AddaVax 作为佐剂,可引发高水平的体液反应。具体而言,用等摩尔的佐剂 CΔ116-NV-CP 融合β-和 δ-变体的 RBD 注射的小鼠增加了 Th 细胞的产生,CD8/CD4 比值为 0.42。该配方还诱导了巨噬细胞和淋巴细胞的增殖。总的来说,这项研究表明,融合了 SARS-CoV-2 RBD 的诺如病毒截断 CP 具有作为基于 VLP 的 COVID-19 疫苗开发的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c114/10001971/f75960e52aeb/ijms-24-04398-g001.jpg

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