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Pan-genome and reverse vaccinology approaches to design multi-epitope vaccine against Epstein-Barr virus associated with colorectal cancer

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Abstract

Epstein-Barr virus (EBV) is a global lymphotropic virus and has been associated with various malignancies, among which colorectal cancer (CRC) is the prevalent one causing mortality worldwide. In the recent past, numerous research efforts have been made to develop a potential vaccine against this virus; however, none is effective possibly due to their low throughput, laboriousness, and lack of sensitivity. In this study, we designed a multi-epitope subunit vaccine that targets latent membrane protein (LMP-2B) of EBV using pan-genome and reverse vaccinology approaches. Twenty-three major histocompatibility complex (MHC) epitopes (five class-I and eighteen class-II) and eight B-cell epitopes, which have been found to be antigenic, immunogenic, and non-toxic, were selected for the vaccine construction. Furthermore, 24 vaccine constructs (VCs) were designed from the predicted epitopes and out of which VC1 was selected and finalized based on its structural parameters. The functionality of VC1 was validated through molecular docking with different immune receptors (MHC class-I, MHC class-II, and TLRs). The binding affinity, molecular and immune simulation revealed that the VC1 had more stable interaction and is believed to elicit good immune responses against EBV.

Highlights

  • Pan-genome and reverse vaccinology approaches were used to design a multi-epitope subunit vaccine against LMP-2B protein of EBV.

  • Epitopes were selected based on the antigenic, immunogenic, and non-toxic properties.

  • Twenty-four vaccine constructs (VCs) were designed from the predicted epitopes.

  • Designed vaccine VC1 has shown good binding affinity and molecular and immune simulation.

  • VC1 was validated using molecular docking with different immune receptors.

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Data availability

All data generated during this study are included in this article.

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Acknowledgements

The authors would like to extend heartfelt gratitude to Prof. (Dr.) Anand Anbarasu (VIT, Vellore) for his guidance in framing the manuscript. P. Priyamvada would like to sincerely thank Dr. Swetha G Rayapadi (ICMR, Research Associate, VIT, Vellore) for her constant support during the manuscript preparation. The authors would like to thank the management of Vellore Institute of Technology (VIT), Vellore, for providing the necessary facilities to carry out this research work.

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The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), the Government of India agency, for the research grant (IRIS ID: 2020–0690).

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  1. Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India

    P. Priyamvada & Sudha Ramaiah

  2. Department of Bio-Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, 632014, Tamil Nadu, India

    P. Priyamvada & Sudha Ramaiah

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Conceptualization, methodology, supervision, and validation of protocol: Sudha Ramaiah. Writing-original draft preparation, visualization, and graphical interpretation: P. Priyamvada.

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Priyamvada, P., Ramaiah, S. Pan-genome and reverse vaccinology approaches to design multi-epitope vaccine against Epstein-Barr virus associated with colorectal cancer. Immunol Res 71, 887–908 (2023). https://doi.org/10.1007/s12026-023-09403-2

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