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Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2

The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the s...

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Autores principales: Chen, Jinni, Huang, Baoying, Deng, Yao, Wang, Wen, Zhai, Chengcheng, Han, Di, Wang, Na, Zhao, Ying, Zhai, Desheng, Tan, Wenjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967269/
https://www.ncbi.nlm.nih.gov/pubmed/36851120
http://dx.doi.org/10.3390/vaccines11020243
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author Chen, Jinni
Huang, Baoying
Deng, Yao
Wang, Wen
Zhai, Chengcheng
Han, Di
Wang, Na
Zhao, Ying
Zhai, Desheng
Tan, Wenjie
author_facet Chen, Jinni
Huang, Baoying
Deng, Yao
Wang, Wen
Zhai, Chengcheng
Han, Di
Wang, Na
Zhao, Ying
Zhai, Desheng
Tan, Wenjie
author_sort Chen, Jinni
collection PubMed
description The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the spike (S) protein of the original virus. Except for the S of SARS-CoV-2, the immunoprotective potential of other structural proteins (nucleocapsid, N; envelope, E; membrane, M) as vaccine target antigens is still unclear and worthy of investigation. In this study, synthetic DNA vaccines encoding four SARS-CoV-2 structural proteins (pS, pN, pE, and pM) were developed, and mice were immunized with three doses via intramuscular injection and electroporation. Notably, co-immunization with two DNA vaccines that expressed the S and N proteins induced higher neutralizing antibodies and was more effective in reducing the SARS-CoV-2 viral load than the S protein alone in mice. In addition, pS co-immunization with either pN or pE + pM induced a higher S protein-specific cellular immunity after three immunizations and caused milder histopathological changes than pS alone post-challenge. The role of the conserved structural proteins of SARS-CoV-2, including the N/E/M proteins, should be investigated further for their applications in vaccine design, such as mRNA vaccines.
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spelling pubmed-99672692023-02-26 Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2 Chen, Jinni Huang, Baoying Deng, Yao Wang, Wen Zhai, Chengcheng Han, Di Wang, Na Zhao, Ying Zhai, Desheng Tan, Wenjie Vaccines (Basel) Article The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the spike (S) protein of the original virus. Except for the S of SARS-CoV-2, the immunoprotective potential of other structural proteins (nucleocapsid, N; envelope, E; membrane, M) as vaccine target antigens is still unclear and worthy of investigation. In this study, synthetic DNA vaccines encoding four SARS-CoV-2 structural proteins (pS, pN, pE, and pM) were developed, and mice were immunized with three doses via intramuscular injection and electroporation. Notably, co-immunization with two DNA vaccines that expressed the S and N proteins induced higher neutralizing antibodies and was more effective in reducing the SARS-CoV-2 viral load than the S protein alone in mice. In addition, pS co-immunization with either pN or pE + pM induced a higher S protein-specific cellular immunity after three immunizations and caused milder histopathological changes than pS alone post-challenge. The role of the conserved structural proteins of SARS-CoV-2, including the N/E/M proteins, should be investigated further for their applications in vaccine design, such as mRNA vaccines. MDPI 2023-01-21 /pmc/articles/PMC9967269/ /pubmed/36851120 http://dx.doi.org/10.3390/vaccines11020243 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Jinni
Huang, Baoying
Deng, Yao
Wang, Wen
Zhai, Chengcheng
Han, Di
Wang, Na
Zhao, Ying
Zhai, Desheng
Tan, Wenjie
Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title_full Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title_fullStr Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title_full_unstemmed Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title_short Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2
title_sort synergistic immunity and protection in mice by co-immunization with dna vaccines encoding the spike protein and other structural proteins of sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967269/
https://www.ncbi.nlm.nih.gov/pubmed/36851120
http://dx.doi.org/10.3390/vaccines11020243
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