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Designing a Novel Multi-epitope T Vaccine for “Targeting Protein for Xklp-2” (TPX2) in Hepatocellular Carcinoma Based on Immunoinformatics Approach

  • Parisa Ghahremanifard
  • Farzaneh Afzali
  • Amin Rostami
  • Zahra Nayeri
  • Bijan Bambai
  • Zarrin MinuchehrEmail author
Article
  • 27 Downloads

Abstract

Hepatocellular carcinoma (HCC) is one of the leading cancer-related deaths worldwide. Recently, studies for HCC treatment are focused on cancer immunotherapy, particularly cancer vaccines, to complete and assist other therapies. TPX2 is a microtubule-associated protein necessary for cell division; therefore, alteration in its expression, especially up regulation, is associated with several human carcinomas such as HCC. In this study, immunoinformatics tools were used to design a rational multi-epitope T vaccine against TPX2 in HCC. Cytotoxic T lymphocytes (CTL) and Helper T lymphocytes (HTL) epitopes were predicted and Maltose-binding protein (MBP) was added to the construct as an adjuvant. Evaluation of vaccine properties was indicated that our construct is stable and immunogenic enough to induce relevant responses besides not being allergic. After predicting the tertiary structure and energy minimization, protein–protein docking and molecular dynamics were performed to calculate the free energy and stability of possible interactions between the vaccine and toll-like receptor 4 (TLR4) to assure that simultaneous complementary responses would be activated by our construct. Finally, Codon optimization and in silico cloning were performed to ensure the vaccine expression efficiency in the desired host.

Keywords

Construct Hepatocellular cancer Immunogenicity Immunotherapeutic In-silico 

Abbreviations

HCC

Hepatocellular carcinoma

MBP

Maltose-binding protein

HBV

Hepatitis B virus

HCV

Hepatitis C virus

TACE

Transarterial chemoembolization

RFA

Radiofrequency ablation

CTL

Cytotoxic T lymphocytes

TPX2

Targeting protein for Xklp-2

HTL

Helper T lymphocytes

TSA

Tumor-specific antigens

TAA

Tumor-associated antigens

MHC

Major histocompatibility complex

GRAVY

Grand average of hydropathicity

E. coli

Escherichia coli

JCAT

Java Codon Adaptation Tool

CAI

Codon Adaptation Index

RMSD

Root mean square deviation

RMSF

Root mean square fluctuation

Notes

Acknowledgements

The financial support of this research project by the National Institute of Genetic Engineering and Biotechnology (NIGEB) of Iran is acknowledged. Also, we would like to thank Dr. Javad Zamani for his contribution in this article.

Author Contributions

ZM, BB and PGH conceptualized the project. FA and P.GH did the analyses and interpreted the data except the data related to docking part which was done by ZN and FA. PGH and AR wrote the manuscript. ZM supported the project (corresponding author). All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

There is no conflict of interest.

Supplementary material

10989_2019_9915_MOESM1_ESM.docx (22 kb)
Supplementary material 1 (DOCX 21 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Systems Biotechnology DepartmentNational Institute of Genetic Engineering and Biotechnology (NIGEB)TehranIran
  2. 2.Medical Biotechnology DepartmentNational Institute of Genetic Engineering and Biotechnology (NIGEB)TehranIran
  3. 3.Pars Silico Bioinformatics LaboratoryTehranIran
  4. 4.Paramedical Sciences DepartmentShahid Beheshti University of Medical SciencesTehranIran

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