title: A novel multi-epitope peptide vaccine against cancer: an in silico approach.
abstract: Cancer immunotherapy has an outstanding position in cancer prevention and treatment. In this kind of therapy, the immune system is activated to eliminate cancerous cells. Multi-epitope peptide cancer vaccines are manifesting as the next generation of cancer immunotherapy. In the present study, we have implemented various strategies to design an efficient multi-epitope vaccine. CD8+ cytolytic T lymphocytes (CTLs) epitopes, which have a pivotal role in cellular immune responses, helper epitopes and adjuvant, are three crucial components of peptide vaccine. CTL epitopes were determined from two high immunogenic protein Wilms tumor-1 (WT1) and human papillomavirus (HPV) E7 by various servers, which apply different algorithms. CTL epitopes were linked together by AAY and HEYGAEALERAG motifs to enhance epitope presentation. Pan HLA DR-binding epitope (PADRE) peptide sequence and helper epitopes, which have defined from Tetanus toxin fragment C (TTFrC) by various servers, were used to induce CD4+ helper T lymphocytes (HTLs) responses. Additionally, helper epitopes were conjugated together via GPGPG motifs that stimulate HTL immunity. Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was employed as an adjuvant to polarize CD4+ T cells toward T-helper 1 to induce strong CTL responses. Moreover, the EAAAK linker was introduced to N and C terminals of HBHA for efficient separation. 3D model of protein was generated and predicted B cell epitopes were determined from the surface of built structure. Our protein contains several linear and conformational B cell epitopes, which suggests the antibody triggering property of this novel vaccine. Hence, our final protein can be used for prophylactic or therapeutic usages, because it can potentially stimulate both cellular and humoral immune responses.
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. Electronic address: n.nezafat@srbiau.ac.ir.
authors: Navid
authors: N
authors: Nezafat
authors: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Younes
authors: Y
authors: Ghasemi
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors: Gholamreza
authors: G
authors: Javadi
authors: Department of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Mohammad Javad
authors: MJ
authors: Khoshnoud
authors: Enzyme Technology Lab., Genetics & Metabolism Research Group, Pasteur Institute of Iran, Tehran, Iran.
authors: Eskandar
authors: E
authors: Omidinia
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology*; D019295:Computational Biology; D003198:Computer Simulation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D008024:Ligands; D010455:Peptides; D022223:Vaccines, Subunit
keywords: Adjuvant; Bioinformatics; CTL response; HTL response; Immunotherapy