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

被引：2

作者：

Jiang, Sheng ^{[1
,2
]}

Wu, Shuting ^{[1
]}

Zhao, Gan ^{[3
]}

He, Yue ^{[3
]}

Bao, Linlin ^{[4
,5
]}

Liu, Jiangning ^{[4
,5
]}

Qin, Chuan ^{[4
,5
]}

Hou, Jiawang ^{[3
]}

Ding, Yuan ^{[3
]}

Cheng, Alex ^{[3
]}

Jiang, Brian ^{[3
]}

Wu, John ^{[3
]}

Yan, Jian ^{[6
]}

Humeau, Laurent ^{[6
]}

Patella, Ami ^{[6
]}

Weiner, David B. ^{[7
]}

Broderick, Kate ^{[6
]}

Wang, Bin ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Med Coll SHMC, Sch Basic Med Sci, Key Lab Med Mol Virol MOE NHC CAMS, Shanghai, Peoples R China

[2] Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai, Peoples R China

[3] Advaccine Biopharmaceut Suzhou Co LTD, Biomed Res Inst Advaccine BRIA, Suzhou, Jiangsu, Peoples R China

[4] Chinese Acad Med Sci, Chinese Minist Hlth, Inst Lab Anim Sci, Key Lab Human Dis Comparat Med,Beijing Key Lab An, Beijing, Peoples R China

[5] Peking Union Med Coll PUMC, Comparat Med Ctr, Beijing, Peoples R China

[6] Inovio Pharmaceut, Plymouth Meeting, PA USA

[7] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA

来源：

HUMAN VACCINES & IMMUNOTHERAPEUTICS | 2022年 / 18卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SARS-CoV-2; COVID-19; spike protein; DNA vaccine; protective response; wild-type sequence; optimizations; VIRAL-INFECTIONS; T-CELLS; VACCINES; IMMUNITY; ANTIBODY;

D O I：

10.1080/21645515.2021.2016201

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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-gamma 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.

引用

页数：11

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