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09.09.2022 | Original Article

Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice

verfasst von: Zhuo-xin Li, Sheng Feng, He Zhang, Xin-yu Zhuang, Chao Shang, Shi-yu Sun, Ji-cheng Han, Yu-biao Xie, Jin-yong Zhang, Wei Wang, Cheng-hui Li, Guan-yu Zhao, Peng-fei Hao, Jun-xian Ma, Yan Gao, Jia-qing Zeng, Ming-yao Tian, Zhuo Ha, Hui-jun Lu, Ning-yi Jin

Erschienen in: Archives of Virology | Ausgabe 12/2022

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Abstract

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic–polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3⁺CD4⁺IFN-gamma⁺) and 2.29 times (CD3⁺CD8⁺IFN-gamma⁺) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 10⁴ times and 10⁶ times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.

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Titel: Immunogenicity and protective efficacy of a DNA vaccine inducing optimal expression of the SARS-CoV-2 S gene in hACE2 mice
verfasst von: Zhuo-xin Li
Sheng Feng
He Zhang
Xin-yu Zhuang
Chao Shang
Shi-yu Sun
Ji-cheng Han
Yu-biao Xie
Jin-yong Zhang
Wei Wang
Cheng-hui Li
Guan-yu Zhao
Peng-fei Hao
Jun-xian Ma
Yan Gao
Jia-qing Zeng
Ming-yao Tian
Zhuo Ha
Hui-jun Lu
Ning-yi Jin
Publikationsdatum: 09.09.2022
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 12/2022
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-022-05562-z

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