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Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice

BACKGROUND: DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines. METHODS: In this study,...

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Autores principales: Liu, Xing-Bo, Yu, Guo-Wei, Gao, Xin-Yu, Huang, Jin-Long, Qin, Li-Ting, Ni, Hong-Bo, Lyu, Chuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981393/
https://www.ncbi.nlm.nih.gov/pubmed/33743745
http://dx.doi.org/10.1186/s12985-021-01536-w
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author Liu, Xing-Bo
Yu, Guo-Wei
Gao, Xin-Yu
Huang, Jin-Long
Qin, Li-Ting
Ni, Hong-Bo
Lyu, Chuang
author_facet Liu, Xing-Bo
Yu, Guo-Wei
Gao, Xin-Yu
Huang, Jin-Long
Qin, Li-Ting
Ni, Hong-Bo
Lyu, Chuang
author_sort Liu, Xing-Bo
collection PubMed
description BACKGROUND: DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines. METHODS: In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination. RESULTS: The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity. CONCLUSION: The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-021-01536-w.
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spelling pubmed-79813932021-03-22 Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice Liu, Xing-Bo Yu, Guo-Wei Gao, Xin-Yu Huang, Jin-Long Qin, Li-Ting Ni, Hong-Bo Lyu, Chuang Virol J Research BACKGROUND: DNA vaccine is one of the research hotspots in veterinary vaccine development. Several advantages, such as cost-effectiveness, ease of design and production, good biocompatibility of plasmid DNA, attractive biosafety, and DNA stability, are found in DNA vaccines. METHODS: In this study, the plasmids expressing bovine herpesvirus 1 (BoHV-1) gB, gC, and gD proteins were mixed at the same mass ratio and adsorbed polyethyleneimine (PEI) magnetic beads with a diameter of 50 nm. Further, the plasmid and PEI magnetic bead polymers were packaged into double carboxyl polyethylene glycol (PEG) 600 to use as a DNA vaccine. The prepared DNA vaccine was employed to vaccinate mice via the intranasal route. The immune responses were evaluated in mice after vaccination. RESULTS: The expression of viral proteins could be largely detected in the lung and rarely in the spleen of mice subjected to a vaccination. The examination of biochemical indicators, anal temperature, and histology indicated that the DNA vaccine was safe in vivo. However, short-time toxicity was observed. The total antibody detected with ELISA in vaccinated mice showed a higher level than PBS, DNA, PEI + DNA, and PBS groups. The antibody level was significantly elevated at the 15th week and started to decrease since the 17th week. The neutralizing antibody titer was significantly higher in DNA vaccine than naked DNA vaccinated animals. The total IgA level was much greater in the DNA vaccine group compared to other component vaccinated groups. The examination of cellular cytokines and the percentage of CD4/CD8 indicated that the prepared DNA vaccine induced a strong cellular immunity. CONCLUSION: The mixed application of plasmids expressing BoHV-1 gB/gC/gD proteins by nano-carrier through intranasal route could effectively activate long-term humoral, cellular, and mucosal immune responses at high levels in mice. These data indicate PEI magnetic beads combining with PEG600 are an efficient vector for plasmid DNA to deliver intranasally as a DNA vaccine candidate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-021-01536-w. BioMed Central 2021-03-21 /pmc/articles/PMC7981393/ /pubmed/33743745 http://dx.doi.org/10.1186/s12985-021-01536-w Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Xing-Bo
Yu, Guo-Wei
Gao, Xin-Yu
Huang, Jin-Long
Qin, Li-Ting
Ni, Hong-Bo
Lyu, Chuang
Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title_full Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title_fullStr Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title_full_unstemmed Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title_short Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
title_sort intranasal delivery of plasmids expressing bovine herpesvirus 1 gb/gc/gd proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981393/
https://www.ncbi.nlm.nih.gov/pubmed/33743745
http://dx.doi.org/10.1186/s12985-021-01536-w
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