Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization
Abstract Background Persistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affe...
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BMC
2025-02-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-024-10343-x |
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| author | Bahareh Bahmani Zahra Amini-bayat Mohammad Mehdi Ranjbar Masoud Hassanzadeh Makoui Amir-Hassan Zarnani |
| author_facet | Bahareh Bahmani Zahra Amini-bayat Mohammad Mehdi Ranjbar Masoud Hassanzadeh Makoui Amir-Hassan Zarnani |
| author_sort | Bahareh Bahmani |
| collection | DOAJ |
| description | Abstract Background Persistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affects millions of women worldwide. Modern therapeutic approaches, such as peptide vaccines, could be promising and have potential for the treatment of the HPV-infected population. Methods A HPV16-E7 multi-epitopic vaccine (MEVE7) was designed to comprise potent CD4 + and CD8 + T cell epitopes and optimally expressed in a prokaryotic expression system. Polyclonal antibodies were generated, and their reactivity with immunizing antigen and native protein in E7 expressing cells (TC-1) was assessed by ELISA and immunofluorescent staining, respectively. The efficacy of the vaccine was assessed in a therapeutic animal model of HPV-induced cancer. Results Our study revealed that the final construct was successfully expressed in E. coli BL21 (DE3)-gold within 4 h of induction as inclusion bodies. Among the tested solubilization buffers, the buffer with a pH of 12 and containing 2 M urea showed the highest solubilization effect. Polyclonal antibodies directed against the E7 multi-epitope vaccine were able to react strongly with the immunizing antigen and E7-bearing cells (TC-1). Immunization of TC-1 tumor-bearing mice with HPV16-E7, markedly delayed tumor growth and propagation. Conclusion The poly-epitope vaccine for HPV16-E7, as expressed and purified in this research, is highly immunogenic and capable of triggering E7-specific antibodies, making it a potential therapeutic HPV vaccine. Further research is needed to optimize the vaccination schedule and assess the E7-specific immune cell profile. |
| format | Article |
| id | doaj-art-da7a60a049534b76a6701f4a160bfe08 |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj-art-da7a60a049534b76a6701f4a160bfe082025-02-09T12:14:48ZengBMCBMC Infectious Diseases1471-23342025-02-0125111410.1186/s12879-024-10343-xDevelopment and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterizationBahareh Bahmani0Zahra Amini-bayat1Mohammad Mehdi Ranjbar2Masoud Hassanzadeh Makoui3Amir-Hassan Zarnani4Department of Immunology, School of Public Health, Tehran University of Medical SciencesDepartment of Biotechnology, Iranian Research Organization for Science and Technology (IROST)Department of Virology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO)Department of Immunology, School of Medicine, Zanjan University of Medical SciencesDepartment of Immunology, School of Public Health, Tehran University of Medical SciencesAbstract Background Persistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affects millions of women worldwide. Modern therapeutic approaches, such as peptide vaccines, could be promising and have potential for the treatment of the HPV-infected population. Methods A HPV16-E7 multi-epitopic vaccine (MEVE7) was designed to comprise potent CD4 + and CD8 + T cell epitopes and optimally expressed in a prokaryotic expression system. Polyclonal antibodies were generated, and their reactivity with immunizing antigen and native protein in E7 expressing cells (TC-1) was assessed by ELISA and immunofluorescent staining, respectively. The efficacy of the vaccine was assessed in a therapeutic animal model of HPV-induced cancer. Results Our study revealed that the final construct was successfully expressed in E. coli BL21 (DE3)-gold within 4 h of induction as inclusion bodies. Among the tested solubilization buffers, the buffer with a pH of 12 and containing 2 M urea showed the highest solubilization effect. Polyclonal antibodies directed against the E7 multi-epitope vaccine were able to react strongly with the immunizing antigen and E7-bearing cells (TC-1). Immunization of TC-1 tumor-bearing mice with HPV16-E7, markedly delayed tumor growth and propagation. Conclusion The poly-epitope vaccine for HPV16-E7, as expressed and purified in this research, is highly immunogenic and capable of triggering E7-specific antibodies, making it a potential therapeutic HPV vaccine. Further research is needed to optimize the vaccination schedule and assess the E7-specific immune cell profile.https://doi.org/10.1186/s12879-024-10343-xHuman papillomavirus 16-E7Multi-epitopeTherapeutic vaccine designRecombinant proteinCervical cancer |
| spellingShingle | Bahareh Bahmani Zahra Amini-bayat Mohammad Mehdi Ranjbar Masoud Hassanzadeh Makoui Amir-Hassan Zarnani Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization BMC Infectious Diseases Human papillomavirus 16-E7 Multi-epitope Therapeutic vaccine design Recombinant protein Cervical cancer |
| title | Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization |
| title_full | Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization |
| title_fullStr | Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization |
| title_full_unstemmed | Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization |
| title_short | Development and evaluation of a novel E7 multi-epitopic vaccine for human papillomavirus type 16: design, expression, purification, and immunological characterization |
| title_sort | development and evaluation of a novel e7 multi epitopic vaccine for human papillomavirus type 16 design expression purification and immunological characterization |
| topic | Human papillomavirus 16-E7 Multi-epitope Therapeutic vaccine design Recombinant protein Cervical cancer |
| url | https://doi.org/10.1186/s12879-024-10343-x |
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