Potent immunogenicity and broad-spectrum protection potential of microneedle array patch-based COVID-19 DNA vaccine candidates encoding dimeric RBD chimera of SARS-CoV and SARS-CoV-2 variants

文献类型： 外文期刊

第一作者： Fan, Feng

作者： Fan, Feng;Zhang, Xin;Zhang, Zhiyu;Ding, Yuan;Wang, Limei;Xu, Xin;Hou, Jiawang;Kou, Zhihua;Zhao, Gan;Wang, Bin;Gao, Xiao-Ming;Pan, Yaying;Gong, Fang-Yuan;Jiang, Lin;Kang, Lingyu;Ha, Zhuo;Lu, Huijun

作者机构：

关键词： COVID-19; SARS-CoV-2; RBD chimera; DNA vaccine; microneedle

期刊名称：EMERGING MICROBES & INFECTIONS （ 影响因子：13.2； 五年影响因子：9.9 ）

ISSN：

年卷期： 2023 年 12 卷 1 期

页码：

收录情况： SCI

摘要： Breakthrough infections by SARS-CoV-2 variants pose a global challenge to COVID-19 pandemic control, and the development of more effective vaccines of broad-spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding receptor-binding domain (RBD) chimera of SARS-CoV-1 and SARS-CoV-2 variants, including pAD1002 (encoding RBDSARS/BA1), pAD1003 (encoding RBDSARS/Beta) and pAD131 (encoding RBDBA1/Beta). Plasmids pAD1002 and pAD131 were far more immunogenic than pAD1003 in terms of eliciting RBD-specific IgG when intramuscularly administered without electroporation. Furthermore, dissolvable microneedle array patches (MAP) greatly enhanced the immunogenicity of these DNA constructs in mice and rabbits. MAP laden with pAD1002 (MAP-1002) significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-gamma(+) effector and memory T cells, and generated T lymphocytes of different homing patterns compared to that induced by electroporated DNA in mice. In consistence with the high titer neutralization results of MAP-1002 antisera against SARS-CoV-2 pseudoviruses, MAP-1002 protected human ACE2-transgenic mice from Omicron BA.1 challenge. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV-1 and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.

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