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

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...

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Bibliographic Details
Published in:Emerging microbes & infections 2023-12, Vol.12 (1), p.2202269-2202269
Main Authors: Fan, Feng, Zhang, Xin, Zhang, Zhiyu, Ding, Yuan, Wang, Limei, Xu, Xin, Pan, Yaying, Gong, Fang-Yuan, Jiang, Lin, Kang, Lingyu, Ha, Zhuo, Lu, Huijun, Hou, Jiawang, Kou, Zhihua, Zhao, Gan, Wang, Bin, Gao, Xiao-Ming
Format: Article
Language:English
Subjects:
Animals
Antibodies, Neutralizing
Antibodies, Viral
Coronaviruses
COVID-19
COVID-19 Vaccines
DNA
DNA vaccine
Humans
Mice
Mice, Transgenic
microneedle
Pandemics
Plasmids
Rabbits
RBD chimera
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severe acute respiratory syndrome-related coronavirus
Spike Glycoprotein, Coronavirus
Vaccines, DNA
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Summary: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 RBD SARS/BA1 ), pAD1003 (encoding RBD SARS/Beta ) and pAD131 (encoding RBD BA1/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-γ + 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.
ISSN:2222-1751
2222-1751
DOI:10.1080/22221751.2023.2202269