Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods
Human papillomavirus types 16 and 18 cause the majority of cervical cancers worldwide. Despite the availability of three prophylactic vaccines based on virus-like particles (VLP) of the major capsid protein (L1), these vaccines are unable to clear an existing infection. Such infected persons experie...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/7/1798 |
| _version_ | 1827732107076567040 |
|---|---|
| author | Alexandru Tîrziu Speranța Avram Leonard Mada Mihaela Crișan-Vida Casiana Popovici Dan Popovici Cosmin Faur Corina Duda-Seiman Virgil Păunescu Corina Vernic |
| author_facet | Alexandru Tîrziu Speranța Avram Leonard Mada Mihaela Crișan-Vida Casiana Popovici Dan Popovici Cosmin Faur Corina Duda-Seiman Virgil Păunescu Corina Vernic |
| author_sort | Alexandru Tîrziu |
| collection | DOAJ |
| description | Human papillomavirus types 16 and 18 cause the majority of cervical cancers worldwide. Despite the availability of three prophylactic vaccines based on virus-like particles (VLP) of the major capsid protein (L1), these vaccines are unable to clear an existing infection. Such infected persons experience an increased risk of neoplastic transformation. To overcome this problem, this study proposes an alternative synthetic long peptide (SLP)-based vaccine for persons already infected, including those with precancerous lesions. This new vaccine was designed to stimulate both CD8+ and CD4+ T cells, providing a robust and long-lasting immune response. The SLP construct includes both HLA class I- and class II-restricted epitopes, identified from IEDB or predicted using NetMHCPan and NetMHCIIPan. None of the SLPs were allergenic nor toxic, based on in silico studies. Population coverage studies provided 98.18% coverage for class I epitopes and 99.81% coverage for class II peptides in the IEDB world population’s allele set. Three-dimensional structure ab initio prediction using Rosetta provided good quality models, which were assessed using PROCHECK and QMEAN4. Molecular docking with toll-like receptor 2 identified potential intrinsic TLR2 agonist activity, while molecular dynamics studies of SLPs in water suggested good stability, with favorable thermodynamic properties. |
| first_indexed | 2024-03-11T00:44:58Z |
| format | Article |
| id | doaj.art-85286688f5844cada161c49e199414c9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:58Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-85286688f5844cada161c49e199414c92023-11-18T20:54:00ZengMDPI AGPharmaceutics1999-49232023-06-01157179810.3390/pharmaceutics15071798Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic MethodsAlexandru Tîrziu0Speranța Avram1Leonard Mada2Mihaela Crișan-Vida3Casiana Popovici4Dan Popovici5Cosmin Faur6Corina Duda-Seiman7Virgil Păunescu8Corina Vernic9Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, RomaniaSyonic SRL, Grigore T Popa Street, No. 81, 300254 Timisoara, RomaniaDepartment of Automation and Computers, Politehnica University of Timisoara, 300006 Timisoara, RomaniaSection of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UKDepartment of Mathematics, University of the West Timişoara, Bd. Vasile Pârvan No. 4, 300223 Timişoara, RomaniaDepartment of Orthopaedic Surgery, University of Medicine and Pharmacy “Victor Babes”, Dropiei Street, No. 7, sc B, ap 8, 300661 Timisoara, RomaniaDepartment of Chemistry and Biology, Faculty of Chemistry, Biology, Geography, West University of Timisoara, 16 Pestalozzi, 300115 Timisoara, RomaniaDepartment of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, RomaniaDepartment of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, RomaniaHuman papillomavirus types 16 and 18 cause the majority of cervical cancers worldwide. Despite the availability of three prophylactic vaccines based on virus-like particles (VLP) of the major capsid protein (L1), these vaccines are unable to clear an existing infection. Such infected persons experience an increased risk of neoplastic transformation. To overcome this problem, this study proposes an alternative synthetic long peptide (SLP)-based vaccine for persons already infected, including those with precancerous lesions. This new vaccine was designed to stimulate both CD8+ and CD4+ T cells, providing a robust and long-lasting immune response. The SLP construct includes both HLA class I- and class II-restricted epitopes, identified from IEDB or predicted using NetMHCPan and NetMHCIIPan. None of the SLPs were allergenic nor toxic, based on in silico studies. Population coverage studies provided 98.18% coverage for class I epitopes and 99.81% coverage for class II peptides in the IEDB world population’s allele set. Three-dimensional structure ab initio prediction using Rosetta provided good quality models, which were assessed using PROCHECK and QMEAN4. Molecular docking with toll-like receptor 2 identified potential intrinsic TLR2 agonist activity, while molecular dynamics studies of SLPs in water suggested good stability, with favorable thermodynamic properties.https://www.mdpi.com/1999-4923/15/7/1798human papillomaviruscervical cancertherapeutic vaccineepitopesmolecular dockingin silico |
| spellingShingle | Alexandru Tîrziu Speranța Avram Leonard Mada Mihaela Crișan-Vida Casiana Popovici Dan Popovici Cosmin Faur Corina Duda-Seiman Virgil Păunescu Corina Vernic Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods Pharmaceutics human papillomavirus cervical cancer therapeutic vaccine epitopes molecular docking in silico |
| title | Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods |
| title_full | Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods |
| title_fullStr | Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods |
| title_full_unstemmed | Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods |
| title_short | Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods |
| title_sort | design of a synthetic long peptide vaccine targeting hpv 16 and 18 using immunoinformatic methods |
| topic | human papillomavirus cervical cancer therapeutic vaccine epitopes molecular docking in silico |
| url | https://www.mdpi.com/1999-4923/15/7/1798 |
| work_keys_str_mv | AT alexandrutirziu designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT sperantaavram designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT leonardmada designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT mihaelacrisanvida designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT casianapopovici designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT danpopovici designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT cosminfaur designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT corinadudaseiman designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT virgilpaunescu designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods AT corinavernic designofasyntheticlongpeptidevaccinetargetinghpv16and18usingimmunoinformaticmethods |