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Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection

The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed...

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Detalles Bibliográficos
Autores principales: Zhao, Zirun, Sun, Ying, Li, Mingchun, Yu, Qilin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611093/
https://www.ncbi.nlm.nih.gov/pubmed/37896925
http://dx.doi.org/10.3390/vaccines11101521
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author Zhao, Zirun
Sun, Ying
Li, Mingchun
Yu, Qilin
author_facet Zhao, Zirun
Sun, Ying
Li, Mingchun
Yu, Qilin
author_sort Zhao, Zirun
collection PubMed
description The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed by transforming the Escherichia coli chassis using a de novo synthetic fragment encoding the protein mChEap1 that was composed of the E. coli OmpA peptide, the fluorescence protein mCherry, the Candida albicans adhesin Eap1, and the C-terminally transmembrane region. The EmEAP1 cells highly exposed the mChEap1 on the cell surface under IPTG induction. The fungal vaccine was then prepared by mixing the EmEAP1 cells with aluminum hydroxide gel and CpG. Fluorescence quantification revealed that the fungal vaccine was stable even after 112 days of storage. After immunization in mice, the vaccine resided in the lymph nodes, inducing the recruitment of CD11c(+) dendritic cells. Moreover, the vaccine strongly activated the CD4(+) T splenocytes and elicited high levels of anti-Eap1 IgG. By the prime-boost immunization, the vaccine prolonged the survival time of the mice infected by the C. albicans cells and attenuated fungal colonization together with inflammation in the kidneys. This study sheds light on the development of synthetic biology-based fungal vaccines for the prevention of life-threatening fungal infections.
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spelling pubmed-106110932023-10-28 Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection Zhao, Zirun Sun, Ying Li, Mingchun Yu, Qilin Vaccines (Basel) Article The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed by transforming the Escherichia coli chassis using a de novo synthetic fragment encoding the protein mChEap1 that was composed of the E. coli OmpA peptide, the fluorescence protein mCherry, the Candida albicans adhesin Eap1, and the C-terminally transmembrane region. The EmEAP1 cells highly exposed the mChEap1 on the cell surface under IPTG induction. The fungal vaccine was then prepared by mixing the EmEAP1 cells with aluminum hydroxide gel and CpG. Fluorescence quantification revealed that the fungal vaccine was stable even after 112 days of storage. After immunization in mice, the vaccine resided in the lymph nodes, inducing the recruitment of CD11c(+) dendritic cells. Moreover, the vaccine strongly activated the CD4(+) T splenocytes and elicited high levels of anti-Eap1 IgG. By the prime-boost immunization, the vaccine prolonged the survival time of the mice infected by the C. albicans cells and attenuated fungal colonization together with inflammation in the kidneys. This study sheds light on the development of synthetic biology-based fungal vaccines for the prevention of life-threatening fungal infections. MDPI 2023-09-25 /pmc/articles/PMC10611093/ /pubmed/37896925 http://dx.doi.org/10.3390/vaccines11101521 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Zirun
Sun, Ying
Li, Mingchun
Yu, Qilin
Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title_full Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title_fullStr Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title_full_unstemmed Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title_short Construction of Candida albicans Adhesin-Exposed Synthetic Cells for Preventing Systemic Fungal Infection
title_sort construction of candida albicans adhesin-exposed synthetic cells for preventing systemic fungal infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611093/
https://www.ncbi.nlm.nih.gov/pubmed/37896925
http://dx.doi.org/10.3390/vaccines11101521
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