As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.

随着COVID-19继续在全球范围内快速传播且变种不断出现，迫切需要开发和部署安全有效的疫苗。在这里，我们开发了一种基于 SARS-CoV-2 刺突 (S) 蛋白的三聚体受体结合域 (RBD) 与铁蛋白形成的纳米粒子 (TF-RBD) 融合的 mRNA 疫苗。与 RBD mRNA 疫苗 (T-RBD) 的三聚体形式相比，肌内注射的 TF-RBD 可引发强大而持久的体液免疫以及偏向 Th1 的细胞反应。在用活 SARS-CoV-2 进一步攻击后，两次注射低剂量 TF-RBD 方案的免疫为 hACE2 转导的小鼠提供了足够的保护。此外，TF-RBD 的 mRNA 模板可以轻松快速地设计成变体疫苗来应对 SARS-CoV-2 突变。 TF-RBD 多价疫苗产生针对 Alpha (B.1.1.7) 和 Beta (B.1.351) 变体的广谱中和抗体。这种基于编码的自组装纳米颗粒三聚体RBD的mRNA疫苗为针对SARS-CoV-2的mRNA疫苗的设计提供了参考。