Abstract
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.
Keywords: DNA vaccine; SARS-CoV-2; animal models; antiviral immunity; protection.
【저자키워드】 SARS-CoV-2, animal models, antiviral immunity, DNA vaccine, protection., 【초록키워드】 COVID-19, Vaccine, COVID-19 vaccine, Trial, Antiviral, COVID-19 pandemic, variants of concern, lung, animal models, anti-SARS-CoV-2, Brain, hACE2, Protein, DNA, T cell, Pulmonary function, Viral, ferret, viral replication, Lungs, vaccine platform, antiviral immunity, Critical, DNA vaccine, T cell response, Neutralizing antibody response, SARS-CoV-2 spike, SARS-CoV-2 S protein, K18-hACE2 transgenic mice, Electroporation, Safe, cDNA, Skeletal muscle, weight loss, Viral antigen, profile, domain, clinical development, neutralizing antibody responses, ferrets, European, immunized, DNA plasmid, robust, identify, caused, form, approved, reduced, effective vaccine, expressing, monomeric, secreted, the SARS-CoV-2, 【제목키워드】 animal model, RBD, protective response, elicit, the SARS-CoV-2,