Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant
Abstract Therapeutic human papillomavirus (HPV) DNA vaccine is an attractive option to control existed HPV infection and related lesions. The two early viral oncoproteins, E6 and E7, are continuously expressed in most HPV-related pre- and cancerous cells, and are ideal targets for therapeutic vaccin...
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BMC
2025-01-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-024-02604-7 |
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| author | Yan Zhou Ting Zhang Zhirong Wang Xuemei Xu |
| author_facet | Yan Zhou Ting Zhang Zhirong Wang Xuemei Xu |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | Abstract Therapeutic human papillomavirus (HPV) DNA vaccine is an attractive option to control existed HPV infection and related lesions. The two early viral oncoproteins, E6 and E7, are continuously expressed in most HPV-related pre- and cancerous cells, and are ideal targets for therapeutic vaccines. We have previously developed an HPV 16 DNA vaccine encoding a modified E7/HSP70 (mE7/HSP70) fusion protein, which demonstrated significant antitumor effects in murine models. In this study, we employed multifaceted approach to enhance the potency of the HPV16 DNA vaccine. Strategies including inserting CpG oligodeoxynucleotide (CpG ODNs) into the vaccine vector backbone, selecting cytokine gene adjuvants, combining plasmids encoding mE6/HSP70 and mE7/HSP70, and utilizing electroporation for vaccination. Our findings revealed that mice immunized with CpG-modified vaccines, coupled with an IL-28B gene adjuvant exhibited heightened antigen-specific CD8+ T cell responses. Additionally, the combination of mE6/HSP70 and mE7/HSP70 plasmids synergistically enhanced the specific CD8+ T cell response. Furthermore, vaccination with CpG-modified mE7/HSP70 and mE6/HSP70 plasmids, alongside the Interleukin-28B (IL-28B) gene adjuvant, generated substantial preventive and therapeutic antitumor effects against HPV E6- and E7-expressing tumors in C57BL/6 mice. These results suggested that integrating these multiple strategies into an HPV DNA vaccine holds promise for effectively controlling HPV infection and related diseases. |
| format | Article |
| id | doaj-art-1444079479d94e7ebab69149eeb32b95 |
| institution | Kabale University |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-1444079479d94e7ebab69149eeb32b952025-01-12T12:08:07ZengBMCVirology Journal1743-422X2025-01-0122111210.1186/s12985-024-02604-7Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvantYan Zhou0Ting Zhang1Zhirong Wang2Xuemei Xu3Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeAbstract Therapeutic human papillomavirus (HPV) DNA vaccine is an attractive option to control existed HPV infection and related lesions. The two early viral oncoproteins, E6 and E7, are continuously expressed in most HPV-related pre- and cancerous cells, and are ideal targets for therapeutic vaccines. We have previously developed an HPV 16 DNA vaccine encoding a modified E7/HSP70 (mE7/HSP70) fusion protein, which demonstrated significant antitumor effects in murine models. In this study, we employed multifaceted approach to enhance the potency of the HPV16 DNA vaccine. Strategies including inserting CpG oligodeoxynucleotide (CpG ODNs) into the vaccine vector backbone, selecting cytokine gene adjuvants, combining plasmids encoding mE6/HSP70 and mE7/HSP70, and utilizing electroporation for vaccination. Our findings revealed that mice immunized with CpG-modified vaccines, coupled with an IL-28B gene adjuvant exhibited heightened antigen-specific CD8+ T cell responses. Additionally, the combination of mE6/HSP70 and mE7/HSP70 plasmids synergistically enhanced the specific CD8+ T cell response. Furthermore, vaccination with CpG-modified mE7/HSP70 and mE6/HSP70 plasmids, alongside the Interleukin-28B (IL-28B) gene adjuvant, generated substantial preventive and therapeutic antitumor effects against HPV E6- and E7-expressing tumors in C57BL/6 mice. These results suggested that integrating these multiple strategies into an HPV DNA vaccine holds promise for effectively controlling HPV infection and related diseases.https://doi.org/10.1186/s12985-024-02604-7CpG oligodeoxynucleotideIL-28B gene adjuvantE7E6HSP70HPV DNA vaccine |
| spellingShingle | Yan Zhou Ting Zhang Zhirong Wang Xuemei Xu Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant Virology Journal CpG oligodeoxynucleotide IL-28B gene adjuvant E7 E6 HSP70 HPV DNA vaccine |
| title | Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant |
| title_full | Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant |
| title_fullStr | Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant |
| title_full_unstemmed | Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant |
| title_short | Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant |
| title_sort | augmented immunogenicity of the hpv16 dna vaccine via dual adjuvant approach integration of cpg odn into plasmid backbone and co administration with il 28b gene adjuvant |
| topic | CpG oligodeoxynucleotide IL-28B gene adjuvant E7 E6 HSP70 HPV DNA vaccine |
| url | https://doi.org/10.1186/s12985-024-02604-7 |
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