State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510182, P. R. China.
ACS Nano. 2021 Feb 23;15(2):2738-2752. doi: 10.1021/acsnano.0c08379. Epub 2021 Jan 19.
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 , 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.
2019 年新型冠状病毒病（COVID-19）大流行是由新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的，它造成了经济损失，并在全球范围内威胁人类健康。这场大流行凸显了对稳定、易于生产和有效的疫苗的迫切需求。SARS-CoV-2 使用刺突蛋白受体结合域（RBD）结合其同源受体血管紧张素转化酶 2（ACE2），并启动膜融合。因此，RBD 是疫苗开发的理想靶标。在这项研究中，我们通过使用 SpyTag-SpyCatcher 系统进行共价偶联，设计了三种不同的 RBD 缀合纳米颗粒疫苗候选物，即 RBD- Ferritin（24 个氨基酸）、RBD-mi3（60 个氨基酸）和 RBD-I53-50（120 个氨基酸）。当用 RBD 缀合的纳米颗粒（NPs）与 AddaVax 或 Sigma 佐剂系统一起免疫小鼠时，产生的抗血清对假病毒和真实病毒的中和活性比用单体 RBD 免疫的小鼠高 8 到 120 倍。最重要的是，用 RBD 缀合的 NPs 免疫的小鼠血清更有效地阻止了 RBD 与 ACE2 的结合，进一步证实了有希望的免疫效果。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，本研究中开发的 SARS-CoV-2 RBD 缀合纳米颗粒是一种有竞争力的疫苗候选物，并且载体纳米颗粒可以作为未来疫苗开发的通用平台。
