Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications
Abstract Coxsackievirus B3 (CVB3) is a major cause of myocarditis and acute pancreatitis, particularly in neonates, in whom infections result in severe symptoms and high mortality rates. Despite the urgent need for effective preventive strategies, no vaccines or therapeutic agents have been develope...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-05643-4 |
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| author | Takafumi Noguchi Anju Miyamori Takeshi Sugimoto Paola Miyazato Hirotaka Ebina |
| author_facet | Takafumi Noguchi Anju Miyamori Takeshi Sugimoto Paola Miyazato Hirotaka Ebina |
| author_sort | Takafumi Noguchi |
| collection | DOAJ |
| description | Abstract Coxsackievirus B3 (CVB3) is a major cause of myocarditis and acute pancreatitis, particularly in neonates, in whom infections result in severe symptoms and high mortality rates. Despite the urgent need for effective preventive strategies, no vaccines or therapeutic agents have been developed. Live-attenuated vaccines hold promise for combating viral infections; however, their pathogenicity must be carefully regulated without compromising immunogenicity. Here, we investigated codon deoptimization and defective viral genomes (DVGs) as strategies to modulate CVB3 pathogenicity, while preserving its immune-activating capacity. Codon-deoptimized CVB3s with increased CpG dinucleotide content in their 3CD region were engineered, leveraging the innate immunostimulatory properties of CpG. These modified CVB3s exhibited attenuated pathogenicity proportional to the level of codon deoptimization and induced protective immunity against wild-type CVB3 (CVB3WT), making them viable live-attenuated vaccine candidates. Additionally, DVGs derived from codon-deoptimized CVB3 demonstrated superior viral interference and enhanced stimulation of neutralizing antibody production compared to DVGs derived from CVB3WT. These findings highlight that CpG-enriched genomes and DVGs are promising tools for regulating viral pathogenicity, enhancing vaccine safety, and developing therapeutic strategies against viral infections. |
| format | Article |
| id | doaj-art-4260c742582a4f44b9a08de2c832a44d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4260c742582a4f44b9a08de2c832a44d2025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-05643-4Codon-deoptimized single-round infectious virus for therapeutic and vaccine applicationsTakafumi Noguchi0Anju Miyamori1Takeshi Sugimoto2Paola Miyazato3Hirotaka Ebina4Virus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, The University of OsakaAbstract Coxsackievirus B3 (CVB3) is a major cause of myocarditis and acute pancreatitis, particularly in neonates, in whom infections result in severe symptoms and high mortality rates. Despite the urgent need for effective preventive strategies, no vaccines or therapeutic agents have been developed. Live-attenuated vaccines hold promise for combating viral infections; however, their pathogenicity must be carefully regulated without compromising immunogenicity. Here, we investigated codon deoptimization and defective viral genomes (DVGs) as strategies to modulate CVB3 pathogenicity, while preserving its immune-activating capacity. Codon-deoptimized CVB3s with increased CpG dinucleotide content in their 3CD region were engineered, leveraging the innate immunostimulatory properties of CpG. These modified CVB3s exhibited attenuated pathogenicity proportional to the level of codon deoptimization and induced protective immunity against wild-type CVB3 (CVB3WT), making them viable live-attenuated vaccine candidates. Additionally, DVGs derived from codon-deoptimized CVB3 demonstrated superior viral interference and enhanced stimulation of neutralizing antibody production compared to DVGs derived from CVB3WT. These findings highlight that CpG-enriched genomes and DVGs are promising tools for regulating viral pathogenicity, enhancing vaccine safety, and developing therapeutic strategies against viral infections.https://doi.org/10.1038/s41598-025-05643-4Live-attenuated vaccinesCodon deoptimizationDefective viral genomesCpG dinucleotideCoxsackievirus B3 |
| spellingShingle | Takafumi Noguchi Anju Miyamori Takeshi Sugimoto Paola Miyazato Hirotaka Ebina Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications Scientific Reports Live-attenuated vaccines Codon deoptimization Defective viral genomes CpG dinucleotide Coxsackievirus B3 |
| title | Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications |
| title_full | Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications |
| title_fullStr | Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications |
| title_full_unstemmed | Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications |
| title_short | Codon-deoptimized single-round infectious virus for therapeutic and vaccine applications |
| title_sort | codon deoptimized single round infectious virus for therapeutic and vaccine applications |
| topic | Live-attenuated vaccines Codon deoptimization Defective viral genomes CpG dinucleotide Coxsackievirus B3 |
| url | https://doi.org/10.1038/s41598-025-05643-4 |
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