Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods
Alexandru Tîrziu,
Speranța Avram,
Leonard Mada,
Mihaela Crișan-Vida,
Casiana Popovici,
Dan Popovici,
Cosmin Faur,
Corina Duda-Seiman,
Virgil Păunescu,
Corina Vernic
Affiliations
Alexandru Tîrziu
Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
Speranța Avram
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania
Leonard Mada
Syonic SRL, Grigore T Popa Street, No. 81, 300254 Timisoara, Romania
Mihaela Crișan-Vida
Department of Automation and Computers, Politehnica University of Timisoara, 300006 Timisoara, Romania
Casiana Popovici
Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Dan Popovici
Department of Mathematics, University of the West Timişoara, Bd. Vasile Pârvan No. 4, 300223 Timişoara, Romania
Cosmin Faur
Department of Orthopaedic Surgery, University of Medicine and Pharmacy “Victor Babes”, Dropiei Street, No. 7, sc B, ap 8, 300661 Timisoara, Romania
Corina Duda-Seiman
Department of Chemistry and Biology, Faculty of Chemistry, Biology, Geography, West University of Timisoara, 16 Pestalozzi, 300115 Timisoara, Romania
Virgil Păunescu
Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
Corina Vernic
Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
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.
