Therapeutic Multi-Epitope Vaccine Construction Using in Silico Strategies Against Hepatocellular Carcinoma

Main Article Content

Versha Shah
Ajay Kumar

Abstract

Hepatocellular carcinoma is a chronic infection with progressing symptoms leading to an advanced stage with no effective therapy other than liver transplantation. Recent studies suggest that drugs such as sorafenib and lenvatinib however can provide some relief to the disease but have failed to provide complete protection. Thus considering all the facts, this study is conducted with an immunoinformatics approach targeting XIAP protein which is the key protein involved in the mechanism of Hepatocellular carcinoma (HCC) disease. The screening of the targeted genome sequence was performed to acquire CTL, HTL, and B-cell epitopes through different tools such as NetMHCPred, NetMHCPan, and BepiPred tool leading to the potential candidates for multi-epitope vaccine. Meanwhile, we also found the physiochemical, immunogenic and allergenicity scores of the filtered epitopes and these epitopes were found to be highly antigenic and immunogenic after validation of all the parameters. Meanwhile, the addition of adjuvant and linkers led to the formation of a strong vaccine construct and therefore the binding force between the final vaccine construct with protein through docking obtained was -905.7kcal/mol. Further in silico cloning and expression of the designed vaccine into the plasmid vector also depicted the good performance of designed vaccine thus making it a good choice for the novel vaccine. Henceforth, a potential therapeutic multi-epitope vaccine construct was found to be efficient and thus can be a promising vaccine that could induce strong immunity against Hepatocellular carcinoma.

Article Details

How to Cite
Versha Shah, & Ajay Kumar. (2023). Therapeutic Multi-Epitope Vaccine Construction Using in Silico Strategies Against Hepatocellular Carcinoma. Journal for ReAttach Therapy and Developmental Diversities, 6(10s(2), 2178–2190. https://doi.org/10.53555/jrtdd.v6i10s(2).2837
Section
Articles
Author Biographies

Versha Shah

 Department of Biotechnology, Faculty of Engineering and Technology, Rama University, G.T.Road, Kanpur, 209217, India. 

Ajay Kumar

Department of Biotechnology, Faculty of Engineering and Technology, Rama University, G.T.Road, Kanpur, 209217, India.

References

Tremosini S, Forner A, Boix L, Vilana R, Bianchi L, Reig M, Rimola J, Rodríguez-Lope C, Ayuso C, Solé M, Bruix J. Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut. 2012 Oct;61(10):1481-7.

Roayaie S, Jibara G, Tabrizian P, Park JW, Yang J, Yan L, Schwartz M, Han G, Izzo F, Chen M, Blanc JF, Johnson P, Kudo M, Roberts LR, Sherman M. The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology. 2015 Aug;62(2):440-51.

Dubey, S.K., Mishra, M.K., Khan, F. et al. (2024).An immunoinformatics study to explore HTL epitopes for fungal pathogen Aspergillus lentulus. J Proteins Proteomics.1-13.

Tang A, Bashir MR, Corwin MT, Cruite I, Dietrich CF, Do RKG, Ehman EC, Fowler KJ, Hussain HK, Jha RC, Karam AR, Mamidipalli A, Marks RM, Mitchell DG, Morgan TA, Ohliger MA, Shah A, Vu KN, Sirlin CB., LI-RADS Evidence Working Group. Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review. Radiology. 2018 Jan;286(1):29-48

Harding JJ, Abu-Zeinah G, Chou JF, Owen DH, Ly M, Lowery MA, Capanu M, Do R, Kemeny NE, O'Reilly EM, Saltz LB, Abou-Alfa GK. Frequency, Morbidity, and Mortality of Bone Metastases in Advanced Hepatocellular Carcinoma. J Natl Compr Canc Netw. 2018 Jan;16(1):50-58. [

Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016 Jul;64(1):106-16.

Gupta S, Kumar A. Design of an Epitope-Based Peptide Vaccine Against Dengue Virus Isolate from Eastern Uttar Pradesh, India. Int J Pept Res Ther. 2022;28(3):91.

Bruix J, Sherman M., American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2.

Wang YG, Wang P, Wang B, Fu ZJ, Zhao WJ, Yan SL. Diabetes mellitus and poorer prognosis in hepatocellular carcinoma: a systematic review and meta-analysis. PLoS One. 2014;9(5):e95485. [

Jain D. Tissue diagnosis of hepatocellular carcinoma. J Clin Exp Hepatol. 2014 Aug;4(Suppl 3):S67-73.

Nash KL, Woodall T, Brown AS, Davies SE, Alexander GJ. Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis. World J Gastroenterol. 2010 Aug 28;16(32):4061-5.

Thiele M, Gluud LL, Fialla AD, Dahl EK, Krag A. Large variations in risk of hepatocellular carcinoma and mortality in treatment naïve hepatitis B patients: systematic review with meta-analyses. PLoS One. 2014;9(9):e107177.

Opo, F.A.D.M., Rahman, M.M., Ahammad, F. et al. Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Sci Rep 11, 4049 (2021).

Abbas R, Larisch S. Targeting XIAP for Promoting Cancer Cell Death-The Story of ARTS and SMAC. Cells. 2020 Mar 9;9(3):663.

Repáraz D, Aparicio B, Llopiz D, Hervás-Stubbs S, Sarobe P. Therapeutic Vaccines against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens? Int J Mol Sci. 2022 Feb 11;23(4):2022.

Tojjari A, Saeed A, Singh M, Cavalcante L, Sahin IH, Saeed A. A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma. Vaccines (Basel). 2023.

Shi YH, Ding WX, Zhou J, He JY, Xu Y, Gambotto AA, Rabinowich H, Fan J, Yin XM. Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. Hepatology. 2008 Aug;48(2):497-507.

Fariya, K., and Ajay K. (2021) An integrative docking and simulation-based approach towards the development of epitope-based vaccine against enterotoxigenic Escherichia coli. Network Modeling Analysis in Health Informatics and Bioinformatics 10(1).

Fariya K., Vivek S., and Ajay K. (2019) Computational Identification and Characterization of Potential T-Cell Epitope for the Utility of Vaccine Design Against Enterotoxigenic Escherichia coli. International Journal of Peptide Research and Therapeutics 25(1).

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 25 (13):1605-12.

Jespersen MC, Peters B, Nielsen M, Marcatili P(2017) BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res.

B. Yao, L. Zhang, S. Liang, C. Zhang. (2012) SVMTriP: A method to predict antigenic epitopes using support vector machine to integrate tri-peptide similarity and propensity. PLoS ONE. 7(9):e45152.

Irini A Doytchinova and Darren R Flower. (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics. 8:4.

Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A (2005)Protein Identification and Analysis Tools on the Expasy Server;

(In) John M. Walker (ed): The Proteomics Protocols Handbook, Humana Press .

pp. 571-607.

Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. and Olson, A. J. (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J. Computational Chemistry 16: 2785-91.

Singh, S., Singh, H., Tuknait, A., Chaudhary, K., Singh, B., Kumaran, S. and Raghava, G.P.S. (2015) PEPstrMOD: structure prediction of peptides containing natural, non-natural and modified residues. Biology Direct 10:73.

Saha, S and Raghava G.P.S. (2006) Prediction of Continuous B-cell Epitopes in an Antigen Using Recurrent Neural Network. Proteins. 1; 65(1):40-8.

Nishat Bano, Ajay Kumar(2023) Immunoinformatics study to explore dengue (DENV-1) proteome to design multi-epitope vaccine construct by using CD4+ epitopes, Journal of Genetic Engineering and Biotechnology,21(1):128.

Motamedi Dehbarez F, Mahmoodi S. (2022) Production of a Novel Multi-Epitope Peptide Vaccine against Hepatocellular Carcinoma. Iran J Med Sci. 47(6):558-565.

Dehbarez Motamedi Fatemeh , Nezafat Navid and Mahmoodi Shirin (2020) In Silico Design of a Novel Multi-Epitope Peptide Vaccine Against Hepatocellular Carcinoma, Letters in Drug Design & Discovery 2020; 17 (9) .

Alsaiari AA, Hakami MA, Alotaibi BS, Alkhalil SS, Hazazi A, Alkhorayef N, Jalal K, Yasmin F. (2023)Rational design of multi-epitope-based vaccine by exploring all dengue virus serotypes proteome: an immunoinformatic approach. Immunol Res. 25.