A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery
Abstract Engineered vector‐based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202303568 |
| _version_ | 1827644379085406208 |
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| author | Yu‐an Li Yanni Sun Yuqin Zhang Quan Li Shifeng Wang Roy Curtiss III Huoying Shi |
| author_facet | Yu‐an Li Yanni Sun Yuqin Zhang Quan Li Shifeng Wang Roy Curtiss III Huoying Shi |
| author_sort | Yu‐an Li |
| collection | DOAJ |
| description | Abstract Engineered vector‐based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge. The genetic circuits are engineered that (1) induce self‐lysis to release foreign antigens into target cells and (2) activate the cytosolic surveillance cGAS‐STING axis by releasing DNA into the cytoplasm. Delayed synthesis of the MazF interferase regulates differential mRNA cleavage, resulting in a 36‐fold increase in the delivery of foreign antigens and modest activation of the inflammasome, which collectively contribute to the marked maturation of antigen‐presenting cells (APCs). Bacteria delivering the protective antigen SaoA exhibits excellent immunogenicity and safety in mouse and pig models, significantly improving the survival rate of animals challenged with multiple serotypes of Streptococcus suis. Thus, the SIRV system enables the effective integration of various modular components and antigen cargos, allowing for the generation of an extensive range of intracellular protein delivery systems using multiple bacterial species in a highly efficient manner. |
| first_indexed | 2024-03-09T18:16:53Z |
| format | Article |
| id | doaj.art-a0d93047864b45dd950a66fe10906e98 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-09T18:16:53Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-a0d93047864b45dd950a66fe10906e982023-11-24T08:40:29ZengWileyAdvanced Science2198-38442023-11-011033n/an/a10.1002/advs.202303568A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen DeliveryYu‐an Li0Yanni Sun1Yuqin Zhang2Quan Li3Shifeng Wang4Roy Curtiss III5Huoying Shi6College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu 225000 ChinaCollege of Veterinary Medicine Yangzhou University Yangzhou Jiangsu 225000 ChinaCollege of Veterinary Medicine Yangzhou University Yangzhou Jiangsu 225000 ChinaCollege of Veterinary Medicine Yangzhou University Yangzhou Jiangsu 225000 ChinaDepartment of Infectious Diseases and Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611‐0880 USADepartment of Infectious Diseases and Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611‐0880 USACollege of Veterinary Medicine Yangzhou University Yangzhou Jiangsu 225000 ChinaAbstract Engineered vector‐based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge. The genetic circuits are engineered that (1) induce self‐lysis to release foreign antigens into target cells and (2) activate the cytosolic surveillance cGAS‐STING axis by releasing DNA into the cytoplasm. Delayed synthesis of the MazF interferase regulates differential mRNA cleavage, resulting in a 36‐fold increase in the delivery of foreign antigens and modest activation of the inflammasome, which collectively contribute to the marked maturation of antigen‐presenting cells (APCs). Bacteria delivering the protective antigen SaoA exhibits excellent immunogenicity and safety in mouse and pig models, significantly improving the survival rate of animals challenged with multiple serotypes of Streptococcus suis. Thus, the SIRV system enables the effective integration of various modular components and antigen cargos, allowing for the generation of an extensive range of intracellular protein delivery systems using multiple bacterial species in a highly efficient manner.https://doi.org/10.1002/advs.202303568cGAS‐STINGcytosolic surveillanceMazF interferaseSalmonella |
| spellingShingle | Yu‐an Li Yanni Sun Yuqin Zhang Quan Li Shifeng Wang Roy Curtiss III Huoying Shi A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery Advanced Science cGAS‐STING cytosolic surveillance MazF interferase Salmonella |
| title | A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery |
| title_full | A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery |
| title_fullStr | A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery |
| title_full_unstemmed | A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery |
| title_short | A Bacterial mRNA‐Lysis‐Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery |
| title_sort | bacterial mrna lysis mediated cargo release vaccine system for regulated cytosolic surveillance and optimized antigen delivery |
| topic | cGAS‐STING cytosolic surveillance MazF interferase Salmonella |
| url | https://doi.org/10.1002/advs.202303568 |
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