T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery
Abstract 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 response...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202303049 |
| _version_ | 1797684922565001216 |
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| author | Jinsong Zhang Jianghua Yang Qianlin Li Ruihao Peng Shoudong Fan Huaimin Yi Yuying Lu Yuanli Peng Haozhen Yan Lidan Sun Jiahai Lu Zeliang Chen |
| author_facet | Jinsong Zhang Jianghua Yang Qianlin Li Ruihao Peng Shoudong Fan Huaimin Yi Yuying Lu Yuanli Peng Haozhen Yan Lidan Sun Jiahai Lu Zeliang Chen |
| author_sort | Jinsong Zhang |
| collection | DOAJ |
| description | Abstract 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 RPT 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, RPT‐constructed nanovaccines elicit more potent cytotoxic T cell and CD4+ T helper 1 (Th1)‐biased immune responses, and generate less anti‐scaffold antibody. Moreover, RPT 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. RPT 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. |
| first_indexed | 2024-03-12T00:36:49Z |
| format | Article |
| id | doaj.art-09b1a2b7f17d4b049923de434e79e28d |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T00:36:49Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-09b1a2b7f17d4b049923de434e79e28d2023-09-15T09:28:59ZengWileyAdvanced Science2198-38442023-09-011026n/an/a10.1002/advs.202303049T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen DeliveryJinsong Zhang0Jianghua Yang1Qianlin Li2Ruihao Peng3Shoudong Fan4Huaimin Yi5Yuying Lu6Yuanli Peng7Haozhen Yan8Lidan Sun9Jiahai Lu10Zeliang Chen11NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Guangzhou 510080 ChinaKey Laboratory of Livestock Infectious Diseases Ministry of Education Shenyang Agricultural University Shenyang 110866 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaLiaoning Technology Innovation Center of Nanomaterials for Antibiotics Reduction and Replacement Fengcheng 118199 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaKey Laboratory of Livestock Infectious Diseases Ministry of Education Shenyang Agricultural University Shenyang 110866 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaOne Health Center of Excellence for Research and Training School of Public Health Sun Yat‐sen University Guangzhou 510080 ChinaAbstract 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 RPT 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, RPT‐constructed nanovaccines elicit more potent cytotoxic T cell and CD4+ T helper 1 (Th1)‐biased immune responses, and generate less anti‐scaffold antibody. Moreover, RPT 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. RPT 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.https://doi.org/10.1002/advs.202303049antigen deliveryprotein engineeringself‐assemblyT cell‐mediated immunitythermostable nanoscaffold |
| spellingShingle | Jinsong Zhang Jianghua Yang Qianlin Li Ruihao Peng Shoudong Fan Huaimin Yi Yuying Lu Yuanli Peng Haozhen Yan Lidan Sun Jiahai Lu Zeliang Chen T Cell Activating Thermostable Self‐Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery Advanced Science antigen delivery protein engineering self‐assembly T cell‐mediated immunity thermostable nanoscaffold |
| 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 | antigen delivery protein engineering self‐assembly T cell‐mediated immunity thermostable nanoscaffold |
| url | https://doi.org/10.1002/advs.202303049 |
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