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Computer-Aided Multi-Epitope Based Vaccine Design Against Monkeypox Virus Surface Protein A30L: An Immunoinformatics Approach

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Abstract

Monkeypox, a viral zoonotic disease resembling smallpox, has emerged as a significant national epidemic primarily in Africa. Nevertheless, the recent global dissemination of this pathogen has engendered apprehension regarding its capacity to metamorphose into a sweeping pandemic. To effectively combat this menace, a multi-epitope vaccine has been meticulously engineered with the specific aim of targeting the cell envelope protein of Monkeypox virus (MPXV), thereby stimulating a potent immunological response while mitigating untoward effects. This new vaccine uses T-cell and B-cell epitopes from a highly antigenic, non-allergenic, non-toxic, conserved, and non-homologous A30L protein to provide protection against the virus. In order to ascertain the vaccine design with the utmost efficacy, protein–protein docking methodologies were employed to anticipate the intricate interactions with Toll-like receptors (TLR) 2, 3, 4, 6, and 8. This meticulous approach led the researchers to discern an optimal vaccine architecture, bolstered by affirmative prognostications derived from both molecular dynamics (MD) simulations and immune simulations. The current research findings indicate that the peptides ATHAAFEYSK, FFIVVATAAV, and MNSLSIFFV exhibited antigenic properties and were determined to be non-allergenic and non-toxic. Through the utilization of codon optimization and in-silico cloning techniques, our investigation revealed that the prospective vaccine exhibited a remarkable expression level within Escherichia coli. Moreover, upon conducting immune simulations, we observed the induction of a robust immune response characterized by elevated levels of both B-cell and T-cell mediated immunity. Moreover, as the initial prediction with in-silico techniques has yielded promising results these epitope-based vaccines can be recommended to in vitro and in silico studies to validate their immunogenic properties.

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Abbreviations

ANN:

Artificial Neural Network

CAI:

Codon Adaptation Index

HCID:

High-Consequence Infectious Diseases

MHC I:

Major Histocompatibility Complex I

MHC II:

Major Histocompatibility Complex II

MPXV:

Monkey Pox Virus

PSSM:

Position Specific Scoring Matrix

SASA:

Solvent Accessible Surface Area

TLR:

Toll Like Receptor

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Acknowledgements

The authors would like to acknowledge the Bioinformatics lab facility, BioNome (https://bionome.in/), Bangalore, 560043, India, for their assistance in the work. The help from Dr. Sameer Sharma and his team, Bioinformatics lab, was greatly helpful in performing MD simulation analysis via Gromacs v2019.4.

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Ramprasadh, S.V., Rajakumar, S., Srinivasan, S. et al. Computer-Aided Multi-Epitope Based Vaccine Design Against Monkeypox Virus Surface Protein A30L: An Immunoinformatics Approach. Protein J 42, 645–663 (2023). https://doi.org/10.1007/s10930-023-10150-4

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