Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates
Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates
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DOI：
10.1021/acsnano.0c08379
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发表时间：
2021-01-19
期刊：
影响因子：
17.1
通讯作者：
Zeng, Mu-Sheng
中科院分区：
文献类型：
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作者：
Kang, Yin-Feng;Sun, Cong;Zeng, Mu-Sheng
由新型SARS-CoV-2冠状病毒引起的2019年新冠肺炎大流行造成了经济损失，威胁到了全球人类健康。这场大流行凸显出迫切需要一种稳定、易于生产和有效的疫苗。SARS-CoV-2利用刺激性蛋白受体结合域(RBD)与其同源受体血管紧张素转换酶2(ACE2)结合，启动膜融合。因此，RBD是疫苗开发的理想目标。在本研究中，我们使用SpyTag-SpyCatcher系统通过共价连接设计了三种不同的RBD偶联纳米颗粒疫苗候选者，即RBD-铁蛋白(24-mer)、RBD-Mi3(60-mer)和RBD-I53-50(120-mer)。当RBD结合纳米粒(NPs)与AddaVax或Sigma佐剂系统联合免疫小鼠时，所产生的抗血清对伪病毒和真病毒的中和活性比单体RBD免疫的小鼠高8-120倍。最重要的是，用RBD结合的NPs免疫的小鼠血清在体外更有效地阻断了RBD与ACE2的结合，进一步证实了这一良好的免疫效果。此外，该疫苗在相对简单的放大和灵活的组装方面具有明显的优势。这些结果表明，本研究开发的SARS-CoV-2 RBD偶联纳米粒是一种具有竞争力的候选疫苗，该载体纳米粒可以作为未来疫苗开发的通用平台。
The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.