Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope
Abstract To relieve the limitations of the human papillomavirus (HPV) vaccines based on L1 capsid protein, vaccine formulations based on RG1 epitope of HPV L2 using various built-in adjuvants are under study. Herein, we describe design and construction of a rejoined peptide (RP) harboring HPV16 RG1...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-43965-3 |
| _version_ | 1797576740904632320 |
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| author | Maryam Mashhadi Abolghasem Shirazi Seyed Mehdi Sadat Setareh Haghighat Farzin Roohvand Arash Arashkia |
| author_facet | Maryam Mashhadi Abolghasem Shirazi Seyed Mehdi Sadat Setareh Haghighat Farzin Roohvand Arash Arashkia |
| author_sort | Maryam Mashhadi Abolghasem Shirazi |
| collection | DOAJ |
| description | Abstract To relieve the limitations of the human papillomavirus (HPV) vaccines based on L1 capsid protein, vaccine formulations based on RG1 epitope of HPV L2 using various built-in adjuvants are under study. Herein, we describe design and construction of a rejoined peptide (RP) harboring HPV16 RG1 epitope fused to TLR4/5 agonists and a tetanus toxoid epitope, which were linked by the (GGGS)3 linker in tandem. In silico analyses indicated the proper physicochemical, immunogenic and safety profile of the RP. Docking analyses on predicted 3D model suggested the effective interaction of TLR4/5 agonists within RP with their corresponding TLRs. Expressing the 1206 bp RP-coding DNA in E. coli produced a 46 kDa protein, and immunization of mice by natively-purified RP in different adjuvant formulations indicated the crucial role of the built-in adjuvants for induction of anti-RG1 responses that could be further enhanced by combination of TLR7 agonist/alum adjuvants. While the TLR4/5 agonists contributed in the elicitation of the Th2-polarized immune responses, combination with TLR7 agonist changed the polarization to the balanced Th1/Th2 immune responses. Indeed, RP + TLR7 agonist/alum adjuvants induced the strongest immune responses that could efficiently neutralize the HPV pseudoviruses, and thus might be a promising formulation for an inexpensive and cross-reactive HPV vaccine. |
| first_indexed | 2024-03-10T21:57:03Z |
| format | Article |
| id | doaj.art-f7e7e945bcdd4b32a448afb51329cf39 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:57:03Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f7e7e945bcdd4b32a448afb51329cf392023-11-19T13:06:34ZengNature PortfolioScientific Reports2045-23222023-10-0113111610.1038/s41598-023-43965-3Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitopeMaryam Mashhadi Abolghasem Shirazi0Seyed Mehdi Sadat1Setareh Haghighat2Farzin Roohvand3Arash Arashkia4Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad UniversityDepartment of Hepatitis, AIDS and Blood borne Diseases, Pasteur Institute of IranDepartment of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad UniversityDepartment of Molecular Virology, Pasteur Institute of IranDepartment of Molecular Virology, Pasteur Institute of IranAbstract To relieve the limitations of the human papillomavirus (HPV) vaccines based on L1 capsid protein, vaccine formulations based on RG1 epitope of HPV L2 using various built-in adjuvants are under study. Herein, we describe design and construction of a rejoined peptide (RP) harboring HPV16 RG1 epitope fused to TLR4/5 agonists and a tetanus toxoid epitope, which were linked by the (GGGS)3 linker in tandem. In silico analyses indicated the proper physicochemical, immunogenic and safety profile of the RP. Docking analyses on predicted 3D model suggested the effective interaction of TLR4/5 agonists within RP with their corresponding TLRs. Expressing the 1206 bp RP-coding DNA in E. coli produced a 46 kDa protein, and immunization of mice by natively-purified RP in different adjuvant formulations indicated the crucial role of the built-in adjuvants for induction of anti-RG1 responses that could be further enhanced by combination of TLR7 agonist/alum adjuvants. While the TLR4/5 agonists contributed in the elicitation of the Th2-polarized immune responses, combination with TLR7 agonist changed the polarization to the balanced Th1/Th2 immune responses. Indeed, RP + TLR7 agonist/alum adjuvants induced the strongest immune responses that could efficiently neutralize the HPV pseudoviruses, and thus might be a promising formulation for an inexpensive and cross-reactive HPV vaccine.https://doi.org/10.1038/s41598-023-43965-3 |
| spellingShingle | Maryam Mashhadi Abolghasem Shirazi Seyed Mehdi Sadat Setareh Haghighat Farzin Roohvand Arash Arashkia Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope Scientific Reports |
| title | Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope |
| title_full | Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope |
| title_fullStr | Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope |
| title_full_unstemmed | Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope |
| title_short | Alum and a TLR7 agonist combined with built-in TLR4 and 5 agonists synergistically enhance immune responses against HPV RG1 epitope |
| title_sort | alum and a tlr7 agonist combined with built in tlr4 and 5 agonists synergistically enhance immune responses against hpv rg1 epitope |
| url | https://doi.org/10.1038/s41598-023-43965-3 |
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