The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started.

由 SARS-CoV-2 引起的 COVID-19 大流行使开发安全有效的疫苗成为重中之重。迄今为止，欧洲和美国当局已批准四种疫苗用于预防 COVID-19，但开发具有改善供应和物流状况的其他疫苗平台仍然是当务之急。在这里，我们报告了一种新型 COVID-19 候选疫苗的临床前评估，该候选疫苗基于对骨骼肌中编码病毒抗原的工程合成 cDNA 进行电穿孔。我们构建了一组表达各种形式的 SARS-CoV-2 刺突 (S) 蛋白的原型 DNA 疫苗，并在动物模型中评估了它们的免疫原性。其中，COVID- eVax——一种编码 SARS-CoV-2 S 蛋白受体结合域 (RBD) 分泌单体形式的 DNA 质粒——诱导了最有效的抗 SARS-CoV-2 中和抗体反应（包括针对当前最常见的关注变体） ) 和强大的 T 细胞反应。在用 SARS-CoV-2 攻击后，免疫的 K18-hACE2 转基因小鼠体重减轻减少，肺功能改善，肺和大脑中的病毒复制减少。COVID- e Vax 为应对 SARS-CoV-2 挑战的雪貂提供了重要保护。总之，本研究将 COVID - e Vax 确定为适合临床开发的理想 COVID-19 候选疫苗。因此，最近开始了一项 I-II 期联合试验。