A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection
Abstract A major challenge in the use of DNA vaccines is efficient DNA delivery in vivo. Establishing a safe and efficient electric transfer method is the key to developing rapid DNA vaccines against emerging infectious diseases. To overcome the complexity of designing new electric transfer machines...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00482-0 |
| _version_ | 1797422237564796928 |
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| author | Tsai-Teng Tzeng Kit Man Chai Kuan-Yin Shen Chia-Yi Yu Shiu-Ju Yang Wan-Chun Huang Hung-Chun Liao Fang-Feng Chiu Horng-Yunn Dou Ching-Len Liao Hsin-Wei Chen Shih-Jen Liu |
| author_facet | Tsai-Teng Tzeng Kit Man Chai Kuan-Yin Shen Chia-Yi Yu Shiu-Ju Yang Wan-Chun Huang Hung-Chun Liao Fang-Feng Chiu Horng-Yunn Dou Ching-Len Liao Hsin-Wei Chen Shih-Jen Liu |
| author_sort | Tsai-Teng Tzeng |
| collection | DOAJ |
| description | Abstract A major challenge in the use of DNA vaccines is efficient DNA delivery in vivo. Establishing a safe and efficient electric transfer method is the key to developing rapid DNA vaccines against emerging infectious diseases. To overcome the complexity of designing new electric transfer machines for DNA delivery, a clinically approved electric transfer machine could be considered as an alternative. Here, we report an electroacupuncture machine-based method for DNA vaccine delivery after intramuscular injection of the COVID-19 DNA vaccine. The S gene of SARS-CoV-2 in the pVAX1 plasmid (pSARS2-S) was used as an antigen in this study. We optimized the clinically used electroacupuncture machine settings for efficient induction of the neutralizing antibody titer after intramuscular injection of pSARS2-S in mice. We found that pSARS2-S immunization at 40 Vpp for 3–5 s could induce high neutralizing antibody titers and Th1-biased immune responses. IFN-γ/TNF-α-secreting CD4+ and CD8+ T cells were also observed in the DNA vaccination group but not in the recombinant protein vaccination group. T-cell epitope mapping shows that the major reactive epitopes were located in the N-terminal domain (a.a. 261–285) and receptor-binding domain (a.a. 352–363). Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. In the preclinical toxicology study, blood biochemistry, hematology, and DNA persistence analysis reveal that the DNA delivery method is safe. Furthermore, the raised antisera could also cross-neutralize different variants of concern. These findings suggest that DNA vaccination using an electroacupuncture machine is feasible for use in humans in the future. |
| first_indexed | 2024-03-09T07:29:20Z |
| format | Article |
| id | doaj.art-7fd244ca7063404a8b9a951aeb84a487 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T07:29:20Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-7fd244ca7063404a8b9a951aeb84a4872023-12-03T06:28:29ZengNature Portfolionpj Vaccines2059-01052022-06-017111210.1038/s41541-022-00482-0A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infectionTsai-Teng Tzeng0Kit Man Chai1Kuan-Yin Shen2Chia-Yi Yu3Shiu-Ju Yang4Wan-Chun Huang5Hung-Chun Liao6Fang-Feng Chiu7Horng-Yunn Dou8Ching-Len Liao9Hsin-Wei Chen10Shih-Jen Liu11National Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesNational Institute of Infectious Diseases and Vaccinology, National Health Research InstitutesAbstract A major challenge in the use of DNA vaccines is efficient DNA delivery in vivo. Establishing a safe and efficient electric transfer method is the key to developing rapid DNA vaccines against emerging infectious diseases. To overcome the complexity of designing new electric transfer machines for DNA delivery, a clinically approved electric transfer machine could be considered as an alternative. Here, we report an electroacupuncture machine-based method for DNA vaccine delivery after intramuscular injection of the COVID-19 DNA vaccine. The S gene of SARS-CoV-2 in the pVAX1 plasmid (pSARS2-S) was used as an antigen in this study. We optimized the clinically used electroacupuncture machine settings for efficient induction of the neutralizing antibody titer after intramuscular injection of pSARS2-S in mice. We found that pSARS2-S immunization at 40 Vpp for 3–5 s could induce high neutralizing antibody titers and Th1-biased immune responses. IFN-γ/TNF-α-secreting CD4+ and CD8+ T cells were also observed in the DNA vaccination group but not in the recombinant protein vaccination group. T-cell epitope mapping shows that the major reactive epitopes were located in the N-terminal domain (a.a. 261–285) and receptor-binding domain (a.a. 352–363). Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. In the preclinical toxicology study, blood biochemistry, hematology, and DNA persistence analysis reveal that the DNA delivery method is safe. Furthermore, the raised antisera could also cross-neutralize different variants of concern. These findings suggest that DNA vaccination using an electroacupuncture machine is feasible for use in humans in the future.https://doi.org/10.1038/s41541-022-00482-0 |
| spellingShingle | Tsai-Teng Tzeng Kit Man Chai Kuan-Yin Shen Chia-Yi Yu Shiu-Ju Yang Wan-Chun Huang Hung-Chun Liao Fang-Feng Chiu Horng-Yunn Dou Ching-Len Liao Hsin-Wei Chen Shih-Jen Liu A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection npj Vaccines |
| title | A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection |
| title_full | A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection |
| title_fullStr | A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection |
| title_full_unstemmed | A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection |
| title_short | A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection |
| title_sort | dna vaccine candidate delivered by an electroacupuncture machine provides protective immunity against sars cov 2 infection |
| url | https://doi.org/10.1038/s41541-022-00482-0 |
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