Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Research Article

In Silico Design of a Novel Multi-Epitope Peptide Vaccine Against Hepatocellular Carcinoma

Author(s): Fatemeh Motamedi Dehbarez, Navid Nezafat and Shirin Mahmoodi*

Volume 17, Issue 9, 2020

Page: [1164 - 1176] Pages: 13

DOI: 10.2174/1570180817999200502030038

Price: $65

Abstract

Background: Hepatocellular Carcinoma (HCC) is a prevalent cancer in the world. As yet, there is no medication for complete treatment of HCC.

Objective: There is a critical need to search for an innovative therapy for HCC. Recently, multiepitope vaccines have been introduced as effective immunotherapy approach against HCC.

Methods: In this research, several immunoinformatics methods were applied to create an original multi-epitope vaccine against HCC consisting of CD8+ cytolytic T lymphocytes (CTLs) epitopes selected from α- fetoprotein (AFP), glypican-3 (GPC3), aspartyl-β-hydroxylase (ASPH); CD4+ helper T lymphocytes (HTLs) epitopes from tetanus toxin fragment C (TTFC), and finally, two tandem repeats of HSP70407-426 were used which stimulated strong innate and adaptive immune responses. All the mentioned parts were connected together by relevant linkers.

Results and Discussions: According to physicochemical, structural, and immunological results, the designed vaccine is stable, non-allergen, antigen; it also has a high-quality 3D structure, and numerous linear and conformational B cell epitopes, whereby this vaccine may stimulate efficient humoral immunity.

Conclusion: Center on the collected results, the designed vaccine potentially can induce cellular and humoral immune responses in HCC cases; nonetheless, the efficiency of vaccine must be approved within in vitro and in vivo immunological analyzes.

Keywords: Hepatocellular carcinoma, immunoinformatics, multi-epitope vaccine, adjuvant, immunotherapy, linker.

« Previous Next »
Graphical Abstract

[1]
Tsuchiya, N.; Yoshikawa, T.; Fujinami, N.; Saito, K.; Mizuno, S.; Sawada, Y.; Endo, I.; Nakatsura, T. Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. OncoImmunology, 2017, 6(10)e1346764
[http://dx.doi.org/10.1080/2162402X.2017.1346764 ] [PMID: 29123959]
[2]
Liu, Q.; Yang, Y.; Tan, X.; Tao, Z.; Adah, D.; Yu, S.; Lu, J.; Zhao, S.; Qin, L.; Qin, L.; Chen, X. Plasmodium parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector. Oncotarget, 2017, 8(15), 24785-24796.
[http://dx.doi.org/10.18632/oncotarget.15806 ] [PMID: 28445973]
[3]
Wang, Q.; Luan, W.; Warren, L.; Kadri, H.; Kim, K.W.; Goz, V.; Blank, S.; Isabel Fiel, M.; Hiotis, S.P. Autologous tumor cell lysate-loaded dendritic cell vaccine inhibited tumor progression in an orthotopic murine model for hepatocellular carcinoma. Ann. Surg. Oncol., 2016, 23(5)(Suppl. 5), 574-582.
[http://dx.doi.org/10.1245/s10434-015-5035-9 ] [PMID: 26786094]
[4]
Arzumanyan, A.; Reis, H.M.; Feitelson, M.A. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat. Rev. Cancer, 2013, 13(2), 123-135.
[http://dx.doi.org/10.1038/nrc3449 ] [PMID: 23344543]
[5]
Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J-F.; de Oliveira, A.C.; Santoro, A.; Raoul, J-L.; Forner, A.; Schwartz, M.; Porta, C.; Zeuzem, S.; Bolondi, L.; Greten, T.F.; Galle, P.R.; Seitz, J.F.; Borbath, I.; Haussinger, D.; Giannaris, T.; Shan, M.; Moscovici, M.; Voliotis, D.; Bruix, J. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med., 2008, 359(4), 378-390.
[http://dx.doi.org/10.1056/NEJMoa0708857 ] [PMID: 18650514]
[6]
Sangro, B.; Gomez-Martin, C.; de la Mata, M.; Iñarrairaegui, M.; Garralda, E.; Barrera, P.; Riezu-Boj, J.I.; Larrea, E.; Alfaro, C.; Sarobe, P.; Lasarte, J.J.; Pérez-Gracia, J.L.; Melero, I.; Prieto, J. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J. Hepatol., 2013, 59(1), 81-88.
[http://dx.doi.org/10.1016/j.jhep.2013.02.022 ] [PMID: 23466307]
[7]
Ma, W.; Gilligan, B.M.; Yuan, J.; Li, T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J. Hematol. Oncol., 2016, 9(1), 47.
[http://dx.doi.org/10.1186/s13045-016-0277-y ] [PMID: 27234522]
[8]
Kasai, K.; Ushio, A.; Kasai, Y.; Sawara, K.; Miyamoto, Y.; Oikawa, K.; Kuroda, H.; Takikawa, Y.; Suzuki, K. Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion. Cancer, 2012, 118(13), 3302-3310.
[http://dx.doi.org/10.1002/cncr.26648 ] [PMID: 22072099]
[9]
Jiang, S.; Liu, Y.; Wang, L.; Duan, C.; Liu, M. A meta-analysis and systematic review: Adjuvant interferon therapy for patients with viral hepatitis-related hepatocellular carcinoma. World J. Surg. Oncol., 2013, 11(1), 240.
[http://dx.doi.org/10.1186/1477-7819-11-240 ] [PMID: 24060218]
[10]
Choi, Y.J.; Park, S-J.; Park, Y-S.; Park, H.S.; Yang, K.M.; Heo, K. EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells. PLoS One, 2018, 13(1)e0190638
[http://dx.doi.org/10.1371/journal.pone.0190638 ] [PMID: 29298343]
[11]
Li, X.; Zhang, Z.; Lin, G.; Gao, Y.; Yan, Z.; Yin, H.; Sun, B.; Wang, F.; Zhang, H.; Chen, H.; Cao, D. Antigen-specific T cell response from dendritic cell vaccination using side population cell-associated antigens targets hepatocellular carcinoma. Tumour Biol., 2016, 37(8), 11267-11278.
[http://dx.doi.org/10.1007/s13277-016-4935-z ] [PMID: 26951511]
[12]
Nakagawa, H; Mizukoshi, E; Kobayashi, E; Tamai, T; Hamana, H; Ozawa, T; Kishi, H; Kitahara, M; Yamashita, T; Arai, K Association between high-avidity t-cell receptors, induced by α- fetoprotein− derived peptides, and anti-tumor effects in patients with hepatocellular carcinoma. Gastroenterology , 2017, 152(6), 1395-1406 . e1310.
[13]
Sawada, Y.; Yoshikawa, T.; Ofuji, K.; Yoshimura, M.; Tsuchiya, N.; Takahashi, M.; Nobuoka, D.; Gotohda, N.; Takahashi, S.; Kato, Y.; Konishi, M.; Kinoshita, T.; Ikeda, M.; Nakachi, K.; Yamazaki, N.; Mizuno, S.; Takayama, T.; Yamao, K.; Uesaka, K.; Furuse, J.; Endo, I.; Nakatsura, T. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. OncoImmunology, 2016, 5(5)e1129483
[http://dx.doi.org/10.1080/2162402X.2015.1129483 ] [PMID: 27467945]
[14]
Butterfield, L.H.; Economou, J.S.; Gamblin, T.C.; Geller, D.A. Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients. J. Transl. Med., 2014, 12(1), 86.
[http://dx.doi.org/10.1186/1479-5876-12-86 ] [PMID: 24708667]
[15]
Longo, V.; Gnoni, A.; Casadei Gardini, A.; Pisconti, S.; Licchetta, A.; Scartozzi, M.; Memeo, R.; Palmieri, V.O.; Aprile, G.; Santini, D.; Nardulli, P.; Silvestris, N.; Brunetti, O. Immunotherapeutic approaches for hepatocellular carcinoma. Oncotarget, 2017, 8(20), 33897-33910.
[http://dx.doi.org/10.18632/oncotarget.15406 ] [PMID: 28420805]
[16]
Sette, A.; Livingston, B.; McKinney, D.; Appella, E.; Fikes, J.; Sidney, J.; Newman, M.; Chesnut, R. The development of multi-epitope vaccines: Epitope identification, vaccine design and clinical evaluation. Biologicals, 2001, 29(3-4), 271-276.
[http://dx.doi.org/10.1006/biol.2001.0297 ] [PMID: 11851327]
[17]
Bijker, M.S.; Melief, C.J.; Offringa, R.; van der Burg, S.H. Design and development of synthetic peptide vaccines: past, present and future. Expert Rev. Vaccines, 2007, 6(4), 591-603.
[http://dx.doi.org/10.1586/14760584.6.4.591 ] [PMID: 17669012]
[18]
Mahmoodi, S.; Nezafat, N.; Barzegar, A.; Negahdaripour, M.; Nikanfar, A.R.; Zarghami, N.; Ghasemi, Y. Harnessing bioinformatics for designing a novel multiepitope peptide vaccine against breast cancer. Curr. Pharm. Biotechnol., 2016, 17(12), 1100-1114.
[http://dx.doi.org/10.2174/1389201017666160914191106 ] [PMID: 27633889]
[19]
Zhou, W-Y.; Shi, Y.; Wu, C.; Zhang, W-J.; Mao, X-H.; Guo, G.; Li, H-X.; Zou, Q-M. Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model. Vaccine, 2009, 27(36), 5013-5019.
[http://dx.doi.org/10.1016/j.vaccine.2009.05.009 ] [PMID: 19446591]
[20]
Lu, Z.; Zuo, B.; Jing, R.; Gao, X.; Rao, Q.; Liu, Z.; Qi, H.; Guo, H.; Yin, H. Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. J. Hepatol., 2017, 67(4), 739-748.
[http://dx.doi.org/10.1016/j.jhep.2017.05.019 ] [PMID: 28549917]
[21]
Lee, J-H.; Lee, Y.; Lee, M.; Heo, M.K.; Song, J-S.; Kim, K-H.; Lee, H.; Yi, N-J.; Lee, K-W.; Suh, K-S.; Bae, Y.S.; Kim, Y.J. A phase I/IIa study of adjuvant immunotherapy with tumour antigen-pulsed dendritic cells in patients with hepatocellular carcinoma. Br. J. Cancer, 2015, 113(12), 1666-1676.
[http://dx.doi.org/10.1038/bjc.2015.430 ] [PMID: 26657650]
[22]
Hong, Y.; Peng, Y.; Guo, Z.S.; Guevara-Patino, J.; Pang, J.; Butterfield, L.H.; Mivechi, N.F.; Munn, D.H.; Bartlett, D.L.; He, Y. Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma. Hepatology, 2014, 59(4), 1448-1458.
[http://dx.doi.org/10.1002/hep.26893 ] [PMID: 24122861]
[23]
Tomimaru, Y.; Mishra, S.; Safran, H.; Charpentier, K.P.; Martin, W.; De Groot, A.S.; Gregory, S.H.; Wands, J.R. Aspartate-β-hydroxylase induces epitope-specific T cell responses in hepatocellular carcinoma. Vaccine, 2015, 33(10), 1256-1266.
[http://dx.doi.org/10.1016/j.vaccine.2015.01.037 ] [PMID: 25629522]
[24]
Aihara, A.; Huang, C.K.; Olsen, M.J.; Lin, Q.; Chung, W.; Tang, Q.; Dong, X.; Wands, J.R. A cell-surface β-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma. Hepatology, 2014, 60(4), 1302-1313.
[http://dx.doi.org/10.1002/hep.27275 ] [PMID: 24954865]
[25]
Shimoda, M.; Tomimaru, Y.; Charpentier, K.P.; Safran, H.; Carlson, R.I.; Wands, J. Tumor progression-related transmembrane protein aspartate-β-hydroxylase is a target for immunotherapy of hepatocellular carcinoma. J. Hepatol., 2012, 56(5), 1129-1135.
[http://dx.doi.org/10.1016/j.jhep.2011.12.016 ] [PMID: 22245894]
[26]
Bi, Y.; Jiang, H.; Wang, P.; Song, B.; Wang, H.; Kong, X.; Li, Z. Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager. Oncotarget, 2017, 8(32), 52866-52876.
[http://dx.doi.org/10.18632/oncotarget.17905 ] [PMID: 28881778]
[27]
Sayem, M.A.; Tomita, Y.; Yuno, A.; Hirayama, M.; Irie, A.; Tsukamoto, H.; Senju, S.; Yuba, E.; Yoshikawa, T.; Kono, K.; Nakatsura, T.; Nishimura, Y. Identification of glypican-3-derived long peptides activating both CD8+ and CD4+ T cells; prolonged overall survival in cancer patients with Th cell response. OncoImmunology, 2015, 5(1)e1062209
[http://dx.doi.org/10.1080/2162402X.2015.1062209 ] [PMID: 26942076]
[28]
Sawada, Y.; Yoshikawa, T.; Shimomura, M.; Iwama, T.; Endo, I.; Nakatsura, T. Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes. Int. J. Oncol., 2015, 46(1), 28-36.
[http://dx.doi.org/10.3892/ijo.2014.2737 ] [PMID: 25354479]
[29]
Flecken, T.; Schmidt, N.; Hild, S.; Gostick, E.; Drognitz, O.; Zeiser, R.; Schemmer, P.; Bruns, H.; Eiermann, T.; Price, D.A.; Blum, H.E.; Neumann-Haefelin, C.; Thimme, R. Immunodominance and functional alterations of tumor-associated antigen-specific CD8+ T-cell responses in hepatocellular carcinoma. Hepatology, 2014, 59(4), 1415-1426.
[http://dx.doi.org/10.1002/hep.26731 ] [PMID: 24002931]
[30]
Khatoon, N.; Pandey, R.K.; Prajapati, V.K. Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach. Sci. Rep., 2017, 7(1), 8285.
[http://dx.doi.org/10.1038/s41598-017-08842-w ] [PMID: 28811600]
[31]
Verma, S.; Sugadev, R.; Kumar, A.; Chandna, S.; Ganju, L.; Bansal, A. Multi-epitope DnaK peptide vaccine against S.Typhi: An in silico approach. Vaccine, 2018, 36(28), 4014-4022.
[http://dx.doi.org/10.1016/j.vaccine.2018.05.106 ] [PMID: 29861180]
[32]
Shah, R.R.; Hassett, K.J.; Brito, L.A. Overview of vaccine adjuvants: Introduction, history, and current status. Vaccine Adjuvants; Springer, 2017, pp. 1-13.
[http://dx.doi.org/10.1007/978-1-4939-6445-1_1]
[33]
Shokouhi, H.; Farahmand, B.; Ghaemi, A.; Mazaheri, V.; Fotouhi, F. Vaccination with three tandem repeats of M2 extracellular domain fused to Leismania major HSP70 protects mice against influenza A virus challenge. Virus Res., 2018, 251, 40-46.
[http://dx.doi.org/10.1016/j.virusres.2018.05.003 ] [PMID: 29730305]
[34]
Asea, A.; Rehli, M.; Kabingu, E.; Boch, J.A.; Baré, O.; Auron, P.E.; Stevenson, M.A.; Calderwood, S.K. Novel signal transduction pathway utilized by extracellular HSP70: Role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem., 2002, 277(17), 15028-15034.
[http://dx.doi.org/10.1074/jbc.M200497200 ] [PMID: 11836257]
[35]
Vabulas, R.M.; Ahmad-Nejad, P.; da Costa, C.; Miethke, T.; Kirschning, C.J.; Häcker, H.; Wagner, H. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J. Biol. Chem., 2001, 276(33), 31332-31339.
[http://dx.doi.org/10.1074/jbc.M103217200 ] [PMID: 11402040]
[36]
Suto, R.; Srivastava, P.K. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science, 1995, 269(5230), 1585-1588.
[http://dx.doi.org/10.1126/science.7545313 ] [PMID: 7545313]
[37]
Shevtsov, M.; Multhoff, G. Heat shock protein-peptide and HSP-based immunotherapies for the treatment of cancer. Front. Immunol., 2016, 7, 171.
[http://dx.doi.org/10.3389/fimmu.2016.00171 ] [PMID: 27199993]
[38]
Li, J.; Xing, Y.; Zhou, Z.; Yao, W.; Cao, R.; Li, T.; Xu, M.; Wu, J. Microbial HSP70 peptide epitope 407-426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer. Tumour Biol., 2016, 37(11), 15097-15105.
[http://dx.doi.org/10.1007/s13277-016-5309-2 ] [PMID: 27662838]
[39]
Xu, M.; Zhang, Y.; Dong, W.; Jiang, L.; Zhang, J.; Yu, P.; Xie, S.; Zhou, L. Two tandem repeats of mHSP70407-426 enhance therapeutic antitumor effects of a recombined vascular endothelial growth factor (VEGF) protein vaccine. Life Sci., 2018, 201, 102-110.
[http://dx.doi.org/10.1016/j.lfs.2018.03.039 ] [PMID: 29572180]
[40]
Zhang, Q; Wang, P; Kim, Y; Haste-Andersen, P; Beaver, J; Bourne, PE; Bui, H-H; Buus, S; Frankild, S Greenbaum, J Immune epitope database analysis resource (IEDB-AR). Nucleic acids research, 2008, 36(suppl_2), W513-W518.
[41]
Parker, K.C.; Bednarek, M.A.; Coligan, J.E. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J. Immunol., 1994, 152(1), 163-175.
[PMID: 8254189]
[42]
Singh, H.; Raghava, G.P. ProPred1: Prediction of promiscuous MHC Class-I binding sites. Bioinformatics, 2003, 19(8), 1009-1014.
[http://dx.doi.org/10.1093/bioinformatics/btg108 ] [PMID: 12761064]
[43]
Guan, P.; Doytchinova, I.A.; Zygouri, C.; Flower, D.R. MHCPred: A server for quantitative prediction of peptide-MHC binding. Nucleic Acids Res., 2003, 31(13), 3621-3624.
[http://dx.doi.org/10.1093/nar/gkg510 ] [PMID: 12824380]
[44]
Reche, P.A.; Glutting, J-P.; Reinherz, E.L. Prediction of MHC class I binding peptides using profile motifs. Hum. Immunol., 2002, 63(9), 701-709.
[http://dx.doi.org/10.1016/S0198-8859(02)00432-9 ] [PMID: 12175724]
[45]
Dhanda, S.K.; Vir, P.; Raghava, G.P. Designing of interferon-gamma inducing MHC class-II binders. Biol. Direct, 2013, 8(1), 30.
[http://dx.doi.org/10.1186/1745-6150-8-30 ] [PMID: 24304645]
[46]
Bhasin, M.; Raghava, G.P. Prediction of CTL epitopes using QM, SVM and ANN techniques. Vaccine, 2004, 22(23-24), 3195-3204.
[http://dx.doi.org/10.1016/j.vaccine.2004.02.005 ] [PMID: 15297074]
[47]
Yamada, A.; Sasada, T.; Noguchi, M.; Itoh, K. Next-generation peptide vaccines for advanced cancer. Cancer Sci., 2013, 104(1), 15-21.
[http://dx.doi.org/10.1111/cas.12050 ] [PMID: 23107418]
[48]
El-Manzalawy, Y.; Dobbs, D.; Honavar, V. Predicting linear B-cell epitopes using string kernels. J. Mol. Recognit., 2008, 21(4), 243-255.
[http://dx.doi.org/10.1002/jmr.893 ] [PMID: 18496882]
[49]
Magnan, C.N.; Zeller, M.; Kayala, M.A.; Vigil, A.; Randall, A.; Felgner, P.L.; Baldi, P. High-throughput prediction of protein antigenicity using protein microarray data. Bioinformatics, 2010, 26(23), 2936-2943.
[http://dx.doi.org/10.1093/bioinformatics/btq551 ] [PMID: 20934990]
[50]
Doytchinova, I.A.; Flower, D.R. VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics, 2007, 8(1), 4.
[http://dx.doi.org/10.1186/1471-2105-8-4 ] [PMID: 17207271]
[51]
Saha, S; Raghava, G AlgPred: Prediction of allergenic proteins and mapping of IgE epitopes. Nucleic Acids Res., 2006, 34(suppl_2), W202-W209.
[http://dx.doi.org/10.1093/nar/gkl343]
[52]
Magnan, C.N.; Randall, A.; Baldi, P. SOLpro: Accurate sequence-based prediction of protein solubility. Bioinformatics, 2009, 25(17), 2200-2207.
[http://dx.doi.org/10.1093/bioinformatics/btp386 ] [PMID: 19549632]
[53]
Gasteiger, E.; Hoogland, C.; Gattiker, A.; Wilkins, M.R.; Appel, R.D.; Bairoch, A. Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook; Springer, 2005, pp. 571-607.
[http://dx.doi.org/10.1385/1-59259-890-0:571]
[54]
Yang, J.; Yan, R.; Roy, A.; Xu, D.; Poisson, J.; Zhang, Y. The I-TASSER Suite: protein structure and function prediction. Nat. Methods, 2015, 12(1), 7-8.
[http://dx.doi.org/10.1038/nmeth.3213 ] [PMID: 25549265]
[55]
Shin, W-H.; Lee, G.R.; Heo, L.; Lee, H.; Seok, C. Prediction of protein structure and interaction by GALAXY protein modeling programs. Bio Design, 2014, 2(1), 1-11.
[56]
Bhattacharya, D.; Nowotny, J.; Cao, R.; Cheng, J. 3Drefine: an interactive web server for efficient protein structure refinement. Nucleic Acids Res., 2016, 44(W1), W406-W409.
[http://dx.doi.org/10.1093/nar/gkw336 ] [PMID: 27131371]
[57]
Lüthy, R.; Bowie, J.U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature, 1992, 356(6364), 83-85.
[http://dx.doi.org/10.1038/356083a0 ] [PMID: 1538787]
[58]
Wiederstein, M; Sippl, MJ ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res.,, 2007, 35(suppl_2), W407-W410.
[http://dx.doi.org/10.1093/nar/gkm290]
[59]
Lovell, S.C.; Davis, I.W.; Arendall, W.B., III; de Bakker, P.I.; Word, J.M.; Prisant, M.G.; Richardson, J.S.; Richardson, D.C. Structure validation by Calpha geometry: ϕ,ψ and Cbeta deviation. Proteins, 2003, 50(3), 437-450.
[http://dx.doi.org/10.1002/prot.10286 ] [PMID: 12557186]
[60]
Kringelum, J.V.; Lundegaard, C.; Lund, O.; Nielsen, M. Reliable B cell epitope predictions: Impacts of method development and improved benchmarking. PLOS Comput. Biol., 2012, 8(12)e1002829
[http://dx.doi.org/10.1371/journal.pcbi.1002829 ] [PMID: 23300419]
[61]
Schmidt, N.; Neumann-Haefelin, C.; Thimme, R. Cellular immune responses to hepatocellular carcinoma: Lessons for immunotherapy. Dig. Dis., 2012, 30(5), 483-491.
[http://dx.doi.org/10.1159/000341697 ] [PMID: 23108304]
[62]
Farhani, I.; Nezafat, N.; Mahmoodi, S. Designing a Novel Multi-epitope peptide vaccine against pathogenic Shigella spp. based immunoinformatics approaches. Int. J. Pept. Res. Ther., 2019, 25(2), 541-553.
[http://dx.doi.org/10.1007/s10989-018-9698-5]
[63]
Nezafat, N.; Eslami, M.; Negahdaripour, M.; Rahbar, M.R.; Ghasemi, Y. Designing an efficient multi-epitope oral vaccine against Helicobacter pylori using immunoinformatics and structural vaccinology approaches. Mol. Biosyst., 2017, 13(4), 699-713.
[http://dx.doi.org/10.1039/C6MB00772D ] [PMID: 28194462]
[64]
Ali, M.; Pandey, R.K.; Khatoon, N.; Narula, A.; Mishra, A.; Prajapati, V.K. Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection. Sci. Rep., 2017, 7(1), 9232.
[http://dx.doi.org/10.1038/s41598-017-09199-w ] [PMID: 28835708]
[65]
Oany, A.R.; Emran, A-A.; Jyoti, T.P. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: An in silico approach. Drug Des. Devel. Ther., 2014, 8, 1139-1149.
[http://dx.doi.org/10.2147/DDDT.S67861 ] [PMID: 25187696]
[66]
Pandey, R.K.; Bhatt, T.K.; Prajapati, V.K. Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating anopheles salivary protein. Sci. Rep., 2018, 8(1), 1125.
[http://dx.doi.org/10.1038/s41598-018-19456-1 ] [PMID: 29348555]
[67]
Pandey, R.K.; Ojha, R.; Aathmanathan, V.S.; Krishnan, M.; Prajapati, V.K. Immunoinformatics approaches to design a novel multi-epitope subunit vaccine against HIV infection. Vaccine, 2018, 36(17), 2262-2272.
[http://dx.doi.org/10.1016/j.vaccine.2018.03.042 ] [PMID: 29571972]
[68]
Hou, G.; Xu, B.; Bi, Y.; Wu, C.; Ru, B.; Sun, B.; Bai, X. Recent advances in research on aspartate β-hydroxylase (ASPH) in pancreatic cancer: A brief update. Bosn. J. Basic Med. Sci., 2018, 18(4), 297-304.
[http://dx.doi.org/10.17305/bjbms.2018.3539 ] [PMID: 30179586]
[69]
Haruyama, Y.; Kataoka, H. Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma. World J. Gastroenterol., 2016, 22(1), 275-283.
[http://dx.doi.org/10.3748/wjg.v22.i1.275 ] [PMID: 26755876]
[70]
Alexander, J.; Fikes, J.; Hoffman, S.; Franke, E.; Sacci, J.; Appella, E.; Chisari, F.V.; Guidotti, L.G.; Chesnut, R.W.; Livingston, B.; Sette, A. The optimization of helper T lymphocyte (HTL) function in vaccine development. Immunol. Res., 1998, 18(2), 79-92.
[http://dx.doi.org/10.1007/BF02788751 ] [PMID: 9844827]
[71]
Validi, M.; Karkhah, A.; Prajapati, V.K.; Nouri, H.R. Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis. Mol. Immunol., 2018, 104, 128-138.
[http://dx.doi.org/10.1016/j.molimm.2018.11.005 ] [PMID: 30448609]
[72]
Aurora, R.; Creamer, T.P.; Srinivasan, R.; Rose, G.D. Local interactions in protein folding: lessons from the α-helix. J. Biol. Chem., 1997, 272(3), 1413-1416.
[http://dx.doi.org/10.1074/jbc.272.3.1413 ] [PMID: 9019474]
[73]
Yano, A.; Onozuka, A.; Asahi-Ozaki, Y.; Imai, S.; Hanada, N.; Miwa, Y.; Nisizawa, T. An ingenious design for peptide vaccines. Vaccine, 2005, 23(17-18), 2322-2326.
[http://dx.doi.org/10.1016/j.vaccine.2005.01.031 ] [PMID: 15755620]
[74]
Negahdaripour, M.; Nezafat, N.; Eslami, M.; Ghoshoon, M.B.; Shoolian, E.; Najafipour, S.; Morowvat, M.H.; Dehshahri, A.; Erfani, N.; Ghasemi, Y. Structural vaccinology considerations for in silico designing of a multi-epitope vaccine. Infect. Genet. Evol., 2018, 58, 96-109.
[http://dx.doi.org/10.1016/j.meegid.2017.12.008 ] [PMID: 29253673]
[75]
Takamatsu, N.; Watanabe, Y.; Yanagi, H.; Meshi, T.; Shiba, T.; Okada, Y. Production of enkephalin in tobacco protoplasts using tobacco mosaic virus RNA vector. FEBS Lett., 1990, 269(1), 73-76.
[http://dx.doi.org/10.1016/0014-5793(90)81121-4 ] [PMID: 2387417]

Rights & Permissions Print Cite
Article Metrics
12
1
© 2024 Bentham Science Publishers | Privacy Policy