The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-S ecto ). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.
【저자키워드】 SARS-CoV-2, DNA vaccines, 【초록키워드】 COVID-19, coronavirus disease, neutralizing antibody, Vaccine, immunization, SARS-CoV-2 vaccine, Spike protein, global pandemic, Spread, Health, Pseudotyped virus, outbreak, mice, SARS-CoV-2 spike glycoprotein, response, T cell responses, vaccine candidate, platform, DNA vaccine, Heterologous, binding, rapid response, coding, trimer, immunogenic, ectodomain, prefusion conformation, Prevent, neutralize, addition, characterized, imperative, specific IgG antibody, the SARS-CoV-2 virus, 【제목키워드】 Vaccine, RNA, mice, induce, anti-SARS-CoV-2 immune response,