Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine

BackgroundCandida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There a...

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Main Authors: Zhao Jin, Yi-Ting Dong, Shuang Liu, Jie Liu, Xi-Ran Qiu, Yu Zhang, Hui Zong, Wei-Tong Hou, Shi-Yu Guo, Yu-Fang Sun, Si-Min Chen, Hai-Qing Dong, Yong-Yong Li, Mao-Mao An, Hui Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.843684/full
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author Zhao Jin
Yi-Ting Dong
Shuang Liu
Jie Liu
Xi-Ran Qiu
Yu Zhang
Hui Zong
Wei-Tong Hou
Shi-Yu Guo
Yu-Fang Sun
Si-Min Chen
Hai-Qing Dong
Yong-Yong Li
Mao-Mao An
Hui Shen
author_facet Zhao Jin
Yi-Ting Dong
Shuang Liu
Jie Liu
Xi-Ran Qiu
Yu Zhang
Hui Zong
Wei-Tong Hou
Shi-Yu Guo
Yu-Fang Sun
Si-Min Chen
Hai-Qing Dong
Yong-Yong Li
Mao-Mao An
Hui Shen
author_sort Zhao Jin
collection DOAJ
description BackgroundCandida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine’s protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells.Materials and MethodsHsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to “charge” the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice.ResultsNanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans.ConclusionAs an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.
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spelling doaj.art-23d975dd68fc465eb022b028a4da268d2022-12-22T00:38:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.843684843684Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal NanovaccineZhao Jin0Yi-Ting Dong1Shuang Liu2Jie Liu3Xi-Ran Qiu4Yu Zhang5Hui Zong6Wei-Tong Hou7Shi-Yu Guo8Yu-Fang Sun9Si-Min Chen10Hai-Qing Dong11Yong-Yong Li12Mao-Mao An13Hui Shen14Department of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, ChinaBackgroundCandida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine’s protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells.Materials and MethodsHsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to “charge” the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice.ResultsNanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans.ConclusionAs an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2022.843684/fullpolyethyleniminenanoparticlesfungal infectionslong-lived plasma celllong-term protection
spellingShingle Zhao Jin
Yi-Ting Dong
Shuang Liu
Jie Liu
Xi-Ran Qiu
Yu Zhang
Hui Zong
Wei-Tong Hou
Shi-Yu Guo
Yu-Fang Sun
Si-Min Chen
Hai-Qing Dong
Yong-Yong Li
Mao-Mao An
Hui Shen
Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
Frontiers in Immunology
polyethylenimine
nanoparticles
fungal infections
long-lived plasma cell
long-term protection
title Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
title_full Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
title_fullStr Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
title_full_unstemmed Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
title_short Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine
title_sort potential of polyethyleneimine as an adjuvant to prepare long term and potent antifungal nanovaccine
topic polyethylenimine
nanoparticles
fungal infections
long-lived plasma cell
long-term protection
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.843684/full
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