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...

Full description

Bibliographic Details
Main Authors: Huang Y, Nan L, Xiao C, Dong J, Li K, Cheng J, Ji Q, Wei Q, Bao G, Liu Y
Format: Article
Language:English
Published: Dove Medical Press 2022-02-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/outer-membrane-vesicles-coating-nano-glycyrrhizic-acid-confers-protect-peer-reviewed-fulltext-article-IJN
_version_ 1818886782742167552
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
first_indexed 2024-12-19T16:26:49Z
format Article
id doaj.art-818b1abdeaf54394a55868be33cbe8e9
institution Directory Open Access Journal
issn 1178-2013
language English
last_indexed 2024-12-19T16:26:49Z
publishDate 2022-02-01
publisher Dove Medical Press
record_format Article
series International Journal of Nanomedicine
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
work_keys_str_mv AT huangy outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT nanl outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT xiaoc outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT dongj outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT lik outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT chengj outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT jiq outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT weiq outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT baog outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses
AT liuy outermembranevesiclescoatingnanoglycyrrhizicacidconfersprotectionagainstborderellabronchisepticathroughth1th2th17responses