SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4⁺ and CD8⁺ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

SARS-CoV-2 感染已成为严重的全球大流行病。由于病毒的高传播性和与 COVID-19 相关的高发病率和死亡率，开发有效和安全的疫苗是首要研究重点。在这里，我们详细评估了脂质纳米颗粒包裹的核苷修饰 mRNA (mRNA-LNP) 疫苗在小鼠体内的免疫原性，该疫苗编码全长 SARS-CoV-2 刺突蛋白或刺突受体结合域。我们证明单剂量的这些疫苗可诱导强 1 型 CD4 ⁺和 CD8 ⁺T 细胞反应，以及长寿命血浆和记忆 B 细胞反应。此外，我们检测到强大且持续的中和抗体反应，并且核苷修饰的 mRNA 疫苗引发的抗体在体外未显示抗体依赖性感染增强。我们的研究结果表明，核苷修饰的 mRNA-LNP 疫苗平台可以诱导强烈的免疫反应，是对抗 COVID-19 的有希望的候选者。