Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses
Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of An...
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Dove Medical Press
2022-02-01
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author | Huang Y Nan L Xiao C Dong J Li K Cheng J Ji Q Wei Q Bao G Liu Y |
author_facet | Huang Y Nan L Xiao C Dong J Li K Cheng J Ji Q Wei Q Bao G Liu Y |
author_sort | Huang Y |
collection | DOAJ |
description | Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infection |
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language | English |
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spelling | doaj.art-818b1abdeaf54394a55868be33cbe8e92022-12-21T20:14:18ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-02-01Volume 1764766372850Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 ResponsesHuang YNan LXiao CDong JLi KCheng JJi QWei QBao GLiu YYee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infectionhttps://www.dovepress.com/outer-membrane-vesicles-coating-nano-glycyrrhizic-acid-confers-protect-peer-reviewed-fulltext-article-IJNouter membrane vesiclesglycyrrhizic acid nanoparticlemacrophageprotective immune responseanti-bacterial infection |
spellingShingle | Huang Y Nan L Xiao C Dong J Li K Cheng J Ji Q Wei Q Bao G Liu Y Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses International Journal of Nanomedicine outer membrane vesicles glycyrrhizic acid nanoparticle macrophage protective immune response anti-bacterial infection |
title | Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses |
title_full | Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses |
title_fullStr | Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses |
title_full_unstemmed | Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses |
title_short | Outer Membrane Vesicles Coating Nano-Glycyrrhizic Acid Confers Protection Against Borderella bronchiseptica Through Th1/Th2/Th17 Responses |
title_sort | outer membrane vesicles coating nano glycyrrhizic acid confers protection against borderella bronchiseptica through th1 th2 th17 responses |
topic | outer membrane vesicles glycyrrhizic acid nanoparticle macrophage protective immune response anti-bacterial infection |
url | https://www.dovepress.com/outer-membrane-vesicles-coating-nano-glycyrrhizic-acid-confers-protect-peer-reviewed-fulltext-article-IJN |
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