Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine
Abstract Antigen uptake, processing, and presentation are crucial for the immune responses of protein‐based vaccines. Herein, we introduced a reversible chemical cross‐linking strategy to engineer protein antigens, which can be tracelessly removed upon antigen‐presenting cell (APC) uptake and cellul...
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| Format: | Article |
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2025-01-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.70045 |
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| author | Long Chen Chao Shang Zihao Wang Mengzhu Zheng Cuiling Zhang Dapeng Li Zhanqun Yang Yuchao Dong Yuru Xu Yunsheng Yuan Shiyong Fan Wu Zhong Jian Lin Xiao Li |
| author_facet | Long Chen Chao Shang Zihao Wang Mengzhu Zheng Cuiling Zhang Dapeng Li Zhanqun Yang Yuchao Dong Yuru Xu Yunsheng Yuan Shiyong Fan Wu Zhong Jian Lin Xiao Li |
| author_sort | Long Chen |
| collection | DOAJ |
| description | Abstract Antigen uptake, processing, and presentation are crucial for the immune responses of protein‐based vaccines. Herein, we introduced a reversible chemical cross‐linking strategy to engineer protein antigens, which can be tracelessly removed upon antigen‐presenting cell (APC) uptake and cellular reduction. The chemically cross‐linked antigen proteins presented significantly enhanced uptake and epitope presentation by APC. We applied this strategy to monkeypox virus antigens A29L and A35R to construct dual‐antigen subunit vaccines. Our results revealed that chemical cross‐linking was robust enough to improve both proteins' APC uptake and lymph node accumulation, with each protein being chemically cross‐linked and administered separately. In vivo validation revealed that the chemical cross‐linking of the two antigen proteins improved immune responses, with increases in antigen‐specific antibody and live virus‐neutralizing antibody production. Monkeypox virus challenge experiments revealed that dual‐antigen vaccines prepared via the chemical cross‐linking strategy mitigated tissue damage, reduced the virus load, and extended mouse survival, which proved that the chemical cross‐linking strategy is valuable for protein‐based subunit vaccine development. In consideration of the current threats from the monkeypox virus and potential future emerging pathogens, the chemical cross‐linking strategy provide powerful tools. |
| format | Article |
| id | doaj-art-72d465026b034bb599e19aad915b8ddf |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-72d465026b034bb599e19aad915b8ddf2025-01-20T01:45:44ZengWileyMedComm2688-26632025-01-0161n/an/a10.1002/mco2.70045Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccineLong Chen0Chao Shang1Zihao Wang2Mengzhu Zheng3Cuiling Zhang4Dapeng Li5Zhanqun Yang6Yuchao Dong7Yuru Xu8Yunsheng Yuan9Shiyong Fan10Wu Zhong11Jian Lin12Xiao Li13Department of Pharmacy Peking University Third Hospital Cancer Center Peking University Third Hospital Beijing ChinaChangchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Changchun ChinaNational Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology Beijing ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education Song Li's Academician Workstation of Hainan University School of Pharmaceutical Sciences Hainan University Haikou ChinaChangchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Changchun ChinaChangchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Changchun ChinaDepartment of Pharmacy Peking University Third Hospital Cancer Center Peking University Third Hospital Beijing ChinaNational Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology Beijing ChinaNational Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology Beijing ChinaEngineering Research Center of Cell & Therapeutic Antibody Ministry of Education Shanghai Jiao Tong University School of Pharmacy Shanghai ChinaNational Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology Beijing ChinaNational Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and Toxicology Beijing ChinaDepartment of Pharmacy Peking University Third Hospital Cancer Center Peking University Third Hospital Beijing ChinaChangchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Changchun ChinaAbstract Antigen uptake, processing, and presentation are crucial for the immune responses of protein‐based vaccines. Herein, we introduced a reversible chemical cross‐linking strategy to engineer protein antigens, which can be tracelessly removed upon antigen‐presenting cell (APC) uptake and cellular reduction. The chemically cross‐linked antigen proteins presented significantly enhanced uptake and epitope presentation by APC. We applied this strategy to monkeypox virus antigens A29L and A35R to construct dual‐antigen subunit vaccines. Our results revealed that chemical cross‐linking was robust enough to improve both proteins' APC uptake and lymph node accumulation, with each protein being chemically cross‐linked and administered separately. In vivo validation revealed that the chemical cross‐linking of the two antigen proteins improved immune responses, with increases in antigen‐specific antibody and live virus‐neutralizing antibody production. Monkeypox virus challenge experiments revealed that dual‐antigen vaccines prepared via the chemical cross‐linking strategy mitigated tissue damage, reduced the virus load, and extended mouse survival, which proved that the chemical cross‐linking strategy is valuable for protein‐based subunit vaccine development. In consideration of the current threats from the monkeypox virus and potential future emerging pathogens, the chemical cross‐linking strategy provide powerful tools.https://doi.org/10.1002/mco2.70045antigen uptake and presentationchemical cross‐linkingdual‐antigenmonkeypox virussubunit vaccine |
| spellingShingle | Long Chen Chao Shang Zihao Wang Mengzhu Zheng Cuiling Zhang Dapeng Li Zhanqun Yang Yuchao Dong Yuru Xu Yunsheng Yuan Shiyong Fan Wu Zhong Jian Lin Xiao Li Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine MedComm antigen uptake and presentation chemical cross‐linking dual‐antigen monkeypox virus subunit vaccine |
| title | Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine |
| title_full | Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine |
| title_fullStr | Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine |
| title_full_unstemmed | Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine |
| title_short | Chemical cross‐linking facilitates antigen uptake and presentation and provides improved protection from Mpox with a dual‐antigen subunit vaccine |
| title_sort | chemical cross linking facilitates antigen uptake and presentation and provides improved protection from mpox with a dual antigen subunit vaccine |
| topic | antigen uptake and presentation chemical cross‐linking dual‐antigen monkeypox virus subunit vaccine |
| url | https://doi.org/10.1002/mco2.70045 |
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