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T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery

Antigen delivery based on non‐virus‐like particle self‐associating protein nanoscffolds, such as Aquifex aeolicus lumazine synthase (AaLS), is limited due to the immunotoxicity and/or premature clearance of antigen‐scaffold complex resulted from triggering unregulated innate immune responses. Here,...

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Autores principales: Zhang, Jinsong, Yang, Jianghua, Li, Qianlin, Peng, Ruihao, Fan, Shoudong, Yi, Huaimin, Lu, Yuying, Peng, Yuanli, Yan, Haozhen, Sun, Lidan, Lu, Jiahai, Chen, Zeliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502629/
https://www.ncbi.nlm.nih.gov/pubmed/37395451
http://dx.doi.org/10.1002/advs.202303049
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author Zhang, Jinsong
Yang, Jianghua
Li, Qianlin
Peng, Ruihao
Fan, Shoudong
Yi, Huaimin
Lu, Yuying
Peng, Yuanli
Yan, Haozhen
Sun, Lidan
Lu, Jiahai
Chen, Zeliang
author_facet Zhang, Jinsong
Yang, Jianghua
Li, Qianlin
Peng, Ruihao
Fan, Shoudong
Yi, Huaimin
Lu, Yuying
Peng, Yuanli
Yan, Haozhen
Sun, Lidan
Lu, Jiahai
Chen, Zeliang
author_sort Zhang, Jinsong
collection PubMed
description Antigen delivery based on non‐virus‐like particle self‐associating protein nanoscffolds, such as Aquifex aeolicus lumazine synthase (AaLS), is limited due to the immunotoxicity and/or premature clearance of antigen‐scaffold complex resulted from triggering unregulated innate immune responses. Here, using rational immunoinformatics prediction and computational modeling, we screen the T epitope peptides from thermophilic nanoproteins with the same spatial structure as hyperthermophilic icosahedral AaLS, and reassemble them into a novel thermostable self‐assembling nanoscaffold RP(T) that can specifically activate T cell‐mediated immunity. Tumor model antigen ovalbumin T epitopes and the severe acute respiratory syndrome coronavirus 2 receptor‐binding domain are loaded onto the scaffold surface through the SpyCather/SpyTag system to construct nanovaccines. Compared to AaLS, RP(T)‐constructed nanovaccines elicit more potent cytotoxic T cell and CD4(+) T helper 1 (Th1)‐biased immune responses, and generate less anti‐scaffold antibody. Moreover, RP(T) significantly upregulate the expression of transcription factors and cytokines related to the differentiation of type‐1 conventional dendritic cells, promoting the cross‐presentation of antigens to CD8(+) T cells and Th1 polarization of CD4(+) T cells. RP(T) confers antigens with increased stability against heating, freeze‐thawing, and lyophilization with almost no antigenicity loss. This novel nanoscaffold offers a simple, safe, and robust strategy for boosting T‐cell immunity‐dependent vaccine development.
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spelling pubmed-105026292023-09-16 T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery Zhang, Jinsong Yang, Jianghua Li, Qianlin Peng, Ruihao Fan, Shoudong Yi, Huaimin Lu, Yuying Peng, Yuanli Yan, Haozhen Sun, Lidan Lu, Jiahai Chen, Zeliang Adv Sci (Weinh) Research Articles Antigen delivery based on non‐virus‐like particle self‐associating protein nanoscffolds, such as Aquifex aeolicus lumazine synthase (AaLS), is limited due to the immunotoxicity and/or premature clearance of antigen‐scaffold complex resulted from triggering unregulated innate immune responses. Here, using rational immunoinformatics prediction and computational modeling, we screen the T epitope peptides from thermophilic nanoproteins with the same spatial structure as hyperthermophilic icosahedral AaLS, and reassemble them into a novel thermostable self‐assembling nanoscaffold RP(T) that can specifically activate T cell‐mediated immunity. Tumor model antigen ovalbumin T epitopes and the severe acute respiratory syndrome coronavirus 2 receptor‐binding domain are loaded onto the scaffold surface through the SpyCather/SpyTag system to construct nanovaccines. Compared to AaLS, RP(T)‐constructed nanovaccines elicit more potent cytotoxic T cell and CD4(+) T helper 1 (Th1)‐biased immune responses, and generate less anti‐scaffold antibody. Moreover, RP(T) significantly upregulate the expression of transcription factors and cytokines related to the differentiation of type‐1 conventional dendritic cells, promoting the cross‐presentation of antigens to CD8(+) T cells and Th1 polarization of CD4(+) T cells. RP(T) confers antigens with increased stability against heating, freeze‐thawing, and lyophilization with almost no antigenicity loss. This novel nanoscaffold offers a simple, safe, and robust strategy for boosting T‐cell immunity‐dependent vaccine development. John Wiley and Sons Inc. 2023-07-03 /pmc/articles/PMC10502629/ /pubmed/37395451 http://dx.doi.org/10.1002/advs.202303049 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhang, Jinsong
Yang, Jianghua
Li, Qianlin
Peng, Ruihao
Fan, Shoudong
Yi, Huaimin
Lu, Yuying
Peng, Yuanli
Yan, Haozhen
Sun, Lidan
Lu, Jiahai
Chen, Zeliang
T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title_full T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title_fullStr T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title_full_unstemmed T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title_short T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
title_sort t cell activating thermostable self‐assembly nanoscaffold tailored for cellular immunity antigen delivery
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502629/
https://www.ncbi.nlm.nih.gov/pubmed/37395451
http://dx.doi.org/10.1002/advs.202303049
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