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. Issue 1 (31st December 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Human vaccines & immunotherapeutics. Volume 18:Issue 1(2022)
• Publication Date: 2022-12-31
• Subjects: SARS-CoV-2 -- COVID-19 -- spike protein -- DNA vaccine -- protective response -- wild-type sequence -- optimizations; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2021.2016201
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: 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.