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

• Published in: Human vaccines & immunotherapeutics Vol. 18; no. 1; p. 2016201
• Main Authors: Jiang, Sheng, Wu, Shuting, Zhao, Gan, He, Yue, Bao, Linlin, Liu, Jiangning, Qin, Chuan, Hou, Jiawang, Ding, Yuan, Cheng, Alex, Jiang, Brian, Wu, John, Yan, Jian, Humeau, Laurent, Patella, Ami, Weiner, David B., Broderick, Kate, Wang, Bin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2022; Taylor & Francis Group
• Subjects: Animals; Antibodies, Neutralizing; Antibodies, Viral; Base Sequence; Coronavirus – Research Paper; COVID-19; COVID-19 - prevention & control; DNA vaccine; Mice; optimizations; protective response; SARS-CoV-2; SARS-CoV-2 - genetics; Spike Glycoprotein, Coronavirus - genetics; spike protein; wild-type sequence; COVID-19; DNA vaccine; wild-type sequence; SARS-CoV-2; protective response; spike protein; optimizations
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2021.2016201

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.