Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC.
Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan, ROC.
Int J Biol Macromol. 2021 Dec 15;193(Pt B):1885-1897. doi: 10.1016/j.ijbiomac.2021.11.020. Epub 2021 Nov 11.
The spike (S) protein is a leading vaccine candidate against SARS-CoV-2 infection. The S1 domain of S protein, which contains a critical receptor-binding domain (RBD) antigen, potentially induces protective immunoreactivities against SARS-CoV-2. In this study, we presented preclinical evaluations of a novel insect cell-derived SARS-CoV-2 recombinant S1 (rS1) protein as a potent COVID-19 vaccine candidate. The native antigenicity of rS1 was characterized by enzyme-linked immunosorbent assay with a neutralizing monoclonal antibody targeting the RBD antigen. To improve its immunogenicity, rS1-adjuvanted with fucoidan/trimethylchitosan nanoparticles (FUC-TMC NPs) and cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) were investigated using a mouse model. The S1-specific immunoglobulin G (IgG) titers, FluoroSpot assay, pseudovirus- and prototype SARS-CoV-2-based neutralization assays were assessed. The results showed that the rS1/CpG/ FUC-TMC NPs (rS1/CpG/NPs) formulation induced a broad-spectrum IgG response with potent, long-lasting, and cross-protective neutralizing activity against the emerging SARS-CoV-2 variant of concern, along with a Th1-biased cellular response. Thus, the rS1/CpG/NPs formulation presents a promising vaccination approach against COVID-19.
刺突（S）蛋白是针对 SARS-CoV-2 感染的主要候选疫苗。S 蛋白的 S1 结构域包含一个关键的受体结合域（RBD）抗原，可能会诱导针对 SARS-CoV-2 的保护性免疫反应。在这项研究中，我们对一种新型昆虫细胞衍生的 SARS-CoV-2 重组 S1（rS1）蛋白作为有效的 COVID-19 候选疫苗进行了临床前评估。rS1 的天然抗原性通过酶联免疫吸附试验（ELISA）进行了表征，该试验使用了针对 RBD 抗原的中和单克隆抗体。为了提高其免疫原性，我们用岩藻聚糖/三甲基壳聚糖纳米粒（FUC-TMC NPs）和胞嘧啶磷酸鸟嘌呤寡脱氧核苷酸（CpG-ODNs）对 rS1 进行了佐剂化，并在小鼠模型中进行了研究。评估了 S1 特异性免疫球蛋白 G（IgG）滴度、FluoroSpot 分析、假病毒和原型 SARS-CoV-2 中和测定。结果表明，rS1/CpG/FUC-TMC NPs（rS1/CpG/NPs）配方诱导了广谱 IgG 反应，具有针对新兴 SARS-CoV-2 关注变体的强大、持久和交叉保护中和活性，以及 Th1 偏向的细胞反应。因此，rS1/CpG/NPs 配方为 COVID-19 提供了一种有前途的疫苗接种方法。
