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An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity
Clostridium perfringens is a common opportunistic pathogen endangering livestock and poultry breeds. Here, using enhanced green fluorescent protein as screening marker, a recombinant lactobacillus tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids of C. perfringens was developed,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735629/ https://www.ncbi.nlm.nih.gov/pubmed/31429624 http://dx.doi.org/10.1080/21505594.2019.1653720 |
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author | Ding, Guojie Bai, Jing Feng, Baohua Wang, Li Qiao, Xinyuan Zhou, Han Jiang, Yanping Cui, Wen Tang, Lijie Li, Yijing Xu, Yigang |
author_facet | Ding, Guojie Bai, Jing Feng, Baohua Wang, Li Qiao, Xinyuan Zhou, Han Jiang, Yanping Cui, Wen Tang, Lijie Li, Yijing Xu, Yigang |
author_sort | Ding, Guojie |
collection | PubMed |
description | Clostridium perfringens is a common opportunistic pathogen endangering livestock and poultry breeds. Here, using enhanced green fluorescent protein as screening marker, a recombinant lactobacillus tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids of C. perfringens was developed, and its immunogenicity in mice was investigated via oral administration. This probiotic vaccine could effectively induce antigen-specific secretory IgA (sIgA)-based mucosal and IgG-based humoral immune responses, and significantly high levels (p< 0.05) of cytokines IL-2, IL-4, IL-10, IL-12, IL-17, and IFN-γ were produced in immunized mice. Moreover, lymphoproliferation and percentage of CD4(+) and CD8(+) T cells significantly increased in mice of the probiotic vaccine group. Challenge experiments were performed in mice with C. perfringens toxinotypes A, C, and D crude toxins to evaluate protection efficiency of the probiotic vaccine, using a commercial inactivated C. perfringens vaccine made by C. perfringens toxinotypes A, C, and D as vaccine control. We observed 80% protection rate in the probiotic vaccine group, which was higher than commercial vaccine group, whereas all mice in control groups died and obvious histopathological changes were observed in liver, spleen, kidney, and intestines of mice. Significantly, we compared the immunogenicity and protection efficiency of lactobacillus constitutive expression system and lactobacillus inducible expression system, and results showed that lactobacillus constitutive expression system has obvious advantages. Our study clearly demonstrated that the probiotics vaccine could effectively induce mucosal, humoral, and cellular immunity, and provide effective protection against C. perfringens toxins, suggesting a promising strategy for the development of oral vaccine against C. perfringens. |
format | Online Article Text |
id | pubmed-6735629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-67356292019-09-16 An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity Ding, Guojie Bai, Jing Feng, Baohua Wang, Li Qiao, Xinyuan Zhou, Han Jiang, Yanping Cui, Wen Tang, Lijie Li, Yijing Xu, Yigang Virulence Research Paper Clostridium perfringens is a common opportunistic pathogen endangering livestock and poultry breeds. Here, using enhanced green fluorescent protein as screening marker, a recombinant lactobacillus tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids of C. perfringens was developed, and its immunogenicity in mice was investigated via oral administration. This probiotic vaccine could effectively induce antigen-specific secretory IgA (sIgA)-based mucosal and IgG-based humoral immune responses, and significantly high levels (p< 0.05) of cytokines IL-2, IL-4, IL-10, IL-12, IL-17, and IFN-γ were produced in immunized mice. Moreover, lymphoproliferation and percentage of CD4(+) and CD8(+) T cells significantly increased in mice of the probiotic vaccine group. Challenge experiments were performed in mice with C. perfringens toxinotypes A, C, and D crude toxins to evaluate protection efficiency of the probiotic vaccine, using a commercial inactivated C. perfringens vaccine made by C. perfringens toxinotypes A, C, and D as vaccine control. We observed 80% protection rate in the probiotic vaccine group, which was higher than commercial vaccine group, whereas all mice in control groups died and obvious histopathological changes were observed in liver, spleen, kidney, and intestines of mice. Significantly, we compared the immunogenicity and protection efficiency of lactobacillus constitutive expression system and lactobacillus inducible expression system, and results showed that lactobacillus constitutive expression system has obvious advantages. Our study clearly demonstrated that the probiotics vaccine could effectively induce mucosal, humoral, and cellular immunity, and provide effective protection against C. perfringens toxins, suggesting a promising strategy for the development of oral vaccine against C. perfringens. Taylor & Francis 2019-08-20 /pmc/articles/PMC6735629/ /pubmed/31429624 http://dx.doi.org/10.1080/21505594.2019.1653720 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Ding, Guojie Bai, Jing Feng, Baohua Wang, Li Qiao, Xinyuan Zhou, Han Jiang, Yanping Cui, Wen Tang, Lijie Li, Yijing Xu, Yigang An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title | An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title_full | An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title_fullStr | An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title_full_unstemmed | An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title_short | An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity |
title_sort | egfp-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids for clostridium perfringens elicits effective anti-toxins protective immunity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735629/ https://www.ncbi.nlm.nih.gov/pubmed/31429624 http://dx.doi.org/10.1080/21505594.2019.1653720 |
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