Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo
Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from...
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| Language: | English |
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MDPI AG
2025-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/94 |
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| author | Sheng Jiang Cheng Zu Bin Wang Yiwei Zhong |
| author_facet | Sheng Jiang Cheng Zu Bin Wang Yiwei Zhong |
| author_sort | Sheng Jiang |
| collection | DOAJ |
| description | Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake. Methods and Results: In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.25. High-content imaging revealed that the S-Cr9T–plasmid complex stably adhered to the cell membrane, leading to enhanced plasmid uptake and transfection. In vivo, S-Cr9T significantly increased antigen expression and triggered a robust immune response, including a threefold increase in IFN-γ secretion and several hundred-fold increases in antibody levels compared to control groups. Conclusions: These findings underscore the potential of S-Cr9T to enhance DNA vaccine efficacy, offering a promising platform for advanced gene therapy and vaccination strategies. |
| format | Article |
| id | doaj-art-30c95223428a40319edc2ec1bb2cf406 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-30c95223428a40319edc2ec1bb2cf4062025-01-24T13:51:55ZengMDPI AGVaccines2076-393X2025-01-011319410.3390/vaccines13010094Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In VivoSheng Jiang0Cheng Zu1Bin Wang2Yiwei Zhong3Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaBackground: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake. Methods and Results: In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.25. High-content imaging revealed that the S-Cr9T–plasmid complex stably adhered to the cell membrane, leading to enhanced plasmid uptake and transfection. In vivo, S-Cr9T significantly increased antigen expression and triggered a robust immune response, including a threefold increase in IFN-γ secretion and several hundred-fold increases in antibody levels compared to control groups. Conclusions: These findings underscore the potential of S-Cr9T to enhance DNA vaccine efficacy, offering a promising platform for advanced gene therapy and vaccination strategies.https://www.mdpi.com/2076-393X/13/1/94DNA vaccinecell-penetrating peptidein vitro expressionin vivo expressionantibody responseT cell response |
| spellingShingle | Sheng Jiang Cheng Zu Bin Wang Yiwei Zhong Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo Vaccines DNA vaccine cell-penetrating peptide in vitro expression in vivo expression antibody response T cell response |
| title | Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo |
| title_full | Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo |
| title_fullStr | Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo |
| title_full_unstemmed | Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo |
| title_short | Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo |
| title_sort | enhancing dna vaccine delivery through stearyl modified cell penetrating peptides improved antigen expression and immune response in vitro and in vivo |
| topic | DNA vaccine cell-penetrating peptide in vitro expression in vivo expression antibody response T cell response |
| url | https://www.mdpi.com/2076-393X/13/1/94 |
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