Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants
Background: Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are c...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/49 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587380118257664 |
|---|---|
| author | Zhongjie Sun Zhongyan Wu Xuncheng Su |
| author_facet | Zhongjie Sun Zhongyan Wu Xuncheng Su |
| author_sort | Zhongjie Sun |
| collection | DOAJ |
| description | Background: Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are currently approved for clinical treatment due to limited efficacy. Our goal is to develop a vaccine that can effectively eliminate tumors caused by HPV. Methods: We genetically fused the chemokine XCL1 with the E6 and E7 proteins of HPV16 to target cDC1 and enhance the vaccine-induced cytotoxic T cell response, ultimately developing a DNA vaccine. Additionally, we screened various interleukins and identified IL-9 as an effective molecular adjuvant for our DNA vaccine. Results: The fusion of Xcl1 significantly improved the quantity and quality of the specific CD8+ T cells. The fusion of Xcl1 also increased immune cell infiltration into the tumor microenvironment. The inclusion of IL-9 significantly elevated the vaccine-induced specific T cell response and enhanced anti-tumor efficacy. IL-9 promotes the formation of central memory T cells. Conclusions: the fusion of Xcl1 and the use of IL-9 as a molecular adjuvant represent promising strategies for vaccine development. |
| format | Article |
| id | doaj-art-acd8108e28214979ad23abbaa9e3605d |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-acd8108e28214979ad23abbaa9e3605d2025-01-24T13:51:46ZengMDPI AGVaccines2076-393X2025-01-011314910.3390/vaccines13010049Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular AdjuvantsZhongjie Sun0Zhongyan Wu1Xuncheng Su2State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, ChinaNewish Biological R&D Center, Wuxi 214111, ChinaState Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, ChinaBackground: Human papillomavirus (HPV) is a prevalent infection affecting both men and women, leading to various cytological lesions. Therapeutic vaccines mount a HPV-specific CD8+ cytotoxic T lymphocyte response, thus clearing HPV-infected cells. However, no therapeutic vaccines targeting HPV are currently approved for clinical treatment due to limited efficacy. Our goal is to develop a vaccine that can effectively eliminate tumors caused by HPV. Methods: We genetically fused the chemokine XCL1 with the E6 and E7 proteins of HPV16 to target cDC1 and enhance the vaccine-induced cytotoxic T cell response, ultimately developing a DNA vaccine. Additionally, we screened various interleukins and identified IL-9 as an effective molecular adjuvant for our DNA vaccine. Results: The fusion of Xcl1 significantly improved the quantity and quality of the specific CD8+ T cells. The fusion of Xcl1 also increased immune cell infiltration into the tumor microenvironment. The inclusion of IL-9 significantly elevated the vaccine-induced specific T cell response and enhanced anti-tumor efficacy. IL-9 promotes the formation of central memory T cells. Conclusions: the fusion of Xcl1 and the use of IL-9 as a molecular adjuvant represent promising strategies for vaccine development.https://www.mdpi.com/2076-393X/13/1/49HPVtherapeutic vaccinesXcl1IL-9 |
| spellingShingle | Zhongjie Sun Zhongyan Wu Xuncheng Su Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants Vaccines HPV therapeutic vaccines Xcl1 IL-9 |
| title | Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants |
| title_full | Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants |
| title_fullStr | Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants |
| title_full_unstemmed | Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants |
| title_short | Developing an Effective Therapeutic HPV Vaccine to Eradicate Large Tumors by Genetically Fusing Xcl1 and Incorporating IL-9 as Molecular Adjuvants |
| title_sort | developing an effective therapeutic hpv vaccine to eradicate large tumors by genetically fusing xcl1 and incorporating il 9 as molecular adjuvants |
| topic | HPV therapeutic vaccines Xcl1 IL-9 |
| url | https://www.mdpi.com/2076-393X/13/1/49 |
| work_keys_str_mv | AT zhongjiesun developinganeffectivetherapeutichpvvaccinetoeradicatelargetumorsbygeneticallyfusingxcl1andincorporatingil9asmolecularadjuvants AT zhongyanwu developinganeffectivetherapeutichpvvaccinetoeradicatelargetumorsbygeneticallyfusingxcl1andincorporatingil9asmolecularadjuvants AT xunchengsu developinganeffectivetherapeutichpvvaccinetoeradicatelargetumorsbygeneticallyfusingxcl1andincorporatingil9asmolecularadjuvants |