Immunoinformatics-based multi-epitope vaccine design for the re-emerging monkeypox virus

Mahour Farzan; Mahan Farzan; Yousef Mirzaei; Sara Aiman; Fatemeh Azadegan-Dehkordi; Nader Bagheri

doi:10.1016/j.intimp.2023.110725

Immunoinformatics-based multi-epitope vaccine design for the re-emerging monkeypox virus

Int Immunopharmacol. 2023 Oct:123:110725. doi: 10.1016/j.intimp.2023.110725. Epub 2023 Aug 7.

Authors

Mahour Farzan¹, Mahan Farzan¹, Yousef Mirzaei², Sara Aiman³, Fatemeh Azadegan-Dehkordi⁴, Nader Bagheri⁵

Affiliations

¹ Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran.
² Department of Medical Biochemical Analysis, Cihan University-Erbil, Kurdistan Region, Iraq.
³ Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China.
⁴ Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: fatemehazadegan@gmail.com.
⁵ Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: n.bagheri1985@gmail.com.

PMID: 37556996
DOI: 10.1016/j.intimp.2023.110725

Abstract

Background: On May 7, 2022, WHO reported a new monkeypox case. By May 2023 over 80,000 cases had been reported worldwide outside previously endemic nations. (This primarily affected the men who have sex with men (MSM) community in rich nations). The present research aims to develop a multi-epitope vaccine for the monkeypox virus (MPXV) using structural and cell surface proteins.

Methods: The first part of the research involved retrieving protein sequences. The Immune Epitope Database (IEDB) was then used to analyze the B and T lymphocyte epitopes. After analyzing the sensitizing properties, toxicity, antigenicity, and molecular binding, appropriate linkers were utilizedto connect selected epitopes to adjuvants, and the structure of the vaccine was formulated. Algorithms from the field of immunoinformatics predicted the secondary and tertiary structures of vaccines. The physical, chemical, and structural properties were refined and validated to achieve maximum stability. Molecular docking and molecular dynamic simulations were subsequently employed to assess the vaccine's efficacy. Afterward, the ability of the vaccine to interact with toll-like receptors 3 and 4 (TLR3 and TLR4) was evaluated. Finally, the optimized sequence was then introduced into the Escherichia coli (E. coli) PET30A + vector.

Results: An immunoinformatics evaluation suggested that such a vaccine might be safe revealed that this vaccine is safe, hydrophilic, temperature- and condition-stable, and can stimulate innate immunity by binding to TLR3 and TLR4.

Conclusion: Our findings suggest that the first step in MPXV pathogenesis is structural and cell surface epitopes. In this study, the most effective and promising epitopes were selected and designed throughprecision servers. Furthermore,through the utilization of multi-epitope structures and a combination of two established adjuvants, this research has the potential to be a landmarkin developing an antiviralvaccine against MPXV. However, additional in vitro and in vivo tests are required to confirm these results.

Keywords: Immunoinformatics; Molecular docking; Molecular dynamics; Monkeypox virus (MPXV); Multi-epitope vaccine.

MeSH terms

Computational Biology / methods
Epitopes, B-Lymphocyte
Epitopes, T-Lymphocyte
Escherichia coli
Homosexuality, Male
Humans
Male
Molecular Docking Simulation
Monkeypox virus*
Sexual and Gender Minorities*
Toll-Like Receptor 3
Toll-Like Receptor 4
Vaccines, Subunit

Substances

Toll-Like Receptor 3
Epitopes, B-Lymphocyte
Toll-Like Receptor 4
Epitopes, T-Lymphocyte
Vaccines, Subunit