Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model
oleh: Sheng Jiang, Shuting Wu, Gan Zhao, Yue He, Linlin Bao, Jiangning Liu, Chuan Qin, Jiawang Hou, Yuan Ding, Alex Cheng, Brian Jiang, John Wu, Jian Yan, Laurent Humeau, Ami Patella, David B. Weiner, Kate Broderick, Bin Wang
| Format: | Article |
|---|---|
| Diterbitkan: | Taylor & Francis Group 2022-01-01 |
Deskripsi
Genetic optimization of Nucleic Acid immunogens is important for potentially improving their immune potency. A COVID-19 DNA vaccine is in phase III clinical trial which is based on a promising highly developable technology platform. Here, we show optimization in mice generating a pGX-9501 DNA vaccine encoding full-length spike protein, which results in induction of potent humoral and cellular immune responses, including neutralizing antibodies, that block hACE2-RBD binding of live CoV2 virus in vitro. Optimization resulted in improved induction of cellular immunity by pGX-9501 as demonstrated by increased IFN-γ expression in both CD8+ and CD4 + T cells and this was associated with more robust antiviral CTL responses compared to unoptimized constructs. Vaccination with pGX-9501 induced subsequent protection against virus challenge in a rigorous hACE2 transgenic mouse model. Overall, pGX-9501 is a promising optimized COVID-19 DNA vaccine candidate inducing humoral and cellular immunity contributing to the vaccine’s protective effects.