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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,...

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Autores principales: Ding, Guojie, Bai, Jing, Feng, Baohua, Wang, Li, Qiao, Xinyuan, Zhou, Han, Jiang, Yanping, Cui, Wen, Tang, Lijie, Li, Yijing, Xu, Yigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
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.
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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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